IMMUTEP LIMITED — Investor Presentation 2021

May 12, 2021

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The global leader in developing LAG-3 therapeutics

Corporate Presentation May 2021 (ASX: IMM, NASDAQ: IMMP)

Notice: Forward Looking Statements

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The purpose of the presentation is to provide an update of the business of Immutep Limited ACN 009 237 889 (ASX:IMM; NASDAQ:IMMP). These slides have been prepared as a presentation aid only and the information they contain may require further explanation and/or clarification. Accordingly, these slides and the information they contain should be read in conjunction with past and future announcements made by Immutep and should not be relied upon as an independent source of information. Please refer to the Company's website and/or the Company’s filings to the ASX and SEC for further information.

The views expressed in this presentation contain information derived from publicly available sources that have not been independently verified. No representation or warranty is made as to the accuracy, completeness or reliability of the information.

Any forward-looking statements in this presentation have been prepared on the basis of a number of assumptions which may prove incorrect and the current intentions, plans, expectations and beliefs about future events are subject to risks, uncertainties and other factors, many of which are outside Immutep’s control. Important factors that could cause actual results to differ materially from assumptions or expectations expressed or implied in this presentation include known and unknown risks. Because actual results could differ materially to assumptions made and Immutep’s current intentions, plans, expectations and beliefs about the future, you are urged to view all forward-looking statements contained in this presentation with caution.

This presentation should not be relied on as a recommendation or forecast by Immutep. Nothing in this presentation should be construed as either an offer to sell or a solicitation of an offer to buy or sell shares in any jurisdiction.

This presentation is authorised for release by the CEO of Immutep Limited.

2

Overview

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Immutep

is an innovative biotechnology company developing novel immunotherapies for cancer and autoimmune diseases

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Global leadership position

in LAG-3 with four product candidates in immuno-oncology and autoimmune diseases

Clinical Potential

Collaboration deals executed with industry leaders

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Corporate Strategy:

To develop product candidates to sell, licence or partner with large pharmaceutical companies at key value inflection points

Immutep’s product candidates have demonstrated clinical potential in a range of indications with high unmet need

3

Directors & Officers

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Grant Chamberlain Non-Executive Director

Russell J. Howard PhD Non-Executive Chairman

Pete A Meyers Non-Executive Director & Deputy Chairman

Scientist, executive manager and entrepreneur; previously CEO of Maxygen & Oakbio, positions at NIH, DNAX, Affymax

Former Chief Financial Officer of Eagle Pharmaceuticals, Inc.; previously CFO of Motif Bio; previously Co-Head of Global Health Care Investment Banking at Deutsche Bank

20+ years in investment banking; current partner of One Ventures; previously Head of Mergers and Acquisitions and Financial Sponsors Australia at Bank of America Merrill Lynch

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Marc Voigt Executive Director & Chief Executive Officer

20+ years in leading positions in finance (e.g. Allianz Group), venture capital and biotech industry, multiple financing & licensing transactions

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Prof. Frédéric Triebel MD PhD, Chief Scientific Officer & Chief Medical Officer

Deanne Miller Chief Operating Officer, General Counsel & Company Secretary

Clinical haematologist, and PhD in immunology (Paris University) and successfully developed several research programs in immunogenetics and immunotherapy, leading to over 144 publications and 16 patents

Lawyer; previous positions at RBC Investor Services, Westpac, Macquarie and ASIC

4

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LAG-3 Overview - The most promising immune checkpoint -

LAG-3 Therapeutic Landscape Overview

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Antagonist Agonist Agonist Depleting AB	Company	Program	Preclinical	Phase I	Phase II	Phase III	Total Trials	Patients
		Eftilagimod Alpha(5)		10	4		14	940
	BMS	Relatlimab		10	27	2	39	10,186
		Ieramilimab		1	4	~~Validation~~ “demonstrate a ~~benefit for~~	5	1,069
	Macrogenics	Tebotelimab		3	3	patients”(6)	6	1321
	Merck & Co. Inc.	MK4280		2	3		5	1080
	B.I.	BI754111		4	1		5	380
	Regeneron(1)	Fianlimab		1	1		2	769
	H-L Roche	RO7247669		1	1		2	575
	Incyte	INCAGN02385		1	1		2	74
	Symphogen(2)	SYM022		3			3	223
	F-star	FS-118		2			2	102
	Tesaro(3)	TSR-033		2			2	75
	Innovent	IBI110		1			1	268
	Xencor	XmAb-22841		1			1	242
		IMP761					--	--
	(4)	GSK2831781 (IMP731)		2	1		3	164

Sources: GlobalData, Company websites, clinicaltrials.gov, and sec.gov, as of May 2021. The green bars above represent programs conducted by Immutep &/or its partners. Total trials includes all active, completed &/or inactive trials. Patient totals are based on estimated total enrolled &/or to be enrolled. Not a complete list of currently existing LAG-3 products.

• 1) As of January 7, 2019 Regeneron is in full control of program and continuing development

• 6

• (https://www.sec.gov/Archives/edgar/data/872589/000110465919000977/a19-1325_18k.htm)

• 2) On 3 Apr. 2020 Les Laboratoires Servier Acquires Symphogen

6

• 3) Tesaro was acquired by and is now part of GSK (www.gsk.com/en-gb/media/press-releases/gsk-completes-acquisition-oftesaro-an-oncology-focused-biopharmaceutical-company/ )

• 4) Includes two completed Phase I studies and one discontinued Phase 2 study (see slide 9)

• 5) Including IITs, two planned trials (MBC trial by EOC and HNSCC trial) and the EAT COVID trial

• 6) RELATIVITY-047 (https://investors.bms.com/iframes/press-releases/press-release-details/2021/Bristol-Myers-Squibb-Announces-RELATIVITY047-a-Trial-Evaluating-Anti-LAG-3-Antibody-Relatlimab-and-Opdivo-nivolumab-in-Patients-with-Previously-Untreated-Metastatic-or-UnresectableMelanoma-Meets-Primary-Endpoint-of-Progression-Free-Survival/default.aspx)

LAG-3 as a Therapeutic Target

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LAG-3, an immune checkpoint, is widely expressed on tumor infiltrating lymphocytes (TILs) and cytotoxic T cells → Prime target for immune therapy

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LAG-3 / MHC Class II Interaction
MHCII
T Cell
APC
LAG-3
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→ Positive regulation of antigen presenting cells ( APCs ) → increase in antigen presentation to cytotoxic CD8[+ ] T cells

→ Negative regulation of LAG-3[+] T Cells

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Notes:

7

• APC: antigen presenting cell

Targeting LAG-3 / MHC II:

Multiple Therapeutics in Numerous Diseases

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IMMUNOSTIMULATION
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IMMUNOSUPPRESSION
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MHC II
Partnered with
LAG525
Antagonistic mAb
LAG-3
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Partnered with
LAG-3
GSK’781
Depleting mAb
T Cell
LAG-3
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RELEVANT Immuno-oncology Viral Infections DISEASES Combination Therapies

RELEVANT Rheumatoid Multiple IBD DISEASES Arthritis Sclerosis

Notes:

8

• APC: antigen presenting cell

Immunotherapy Pipeline*

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	Oncology Autoimm. Inf. Dis.	Program	Preclinical	Phase I	Phase II	Late Stage(5)	Commercial Rights	Market Size(6)
		Eftilagimod Alpha (efti or IMP321) APC activating soluble LAG-3 protein	Metastatic Breast Cancer (C AIPAC	hemo – IO)			Global Rights	US$29.9 billion
			Non-Small-Cell Lung Carci TACTI-002	noma (IO – IO)(1)				US$22.6 billion
			Head and Neck Squamous TACTI-002	Cell Carcinoma (IO – IO)(1)				US$1.9 billion
			Head and Neck Squamous TACTI-003	Cell Carcinoma (IO – IO)(1b)
			Solid Tumors (IO – IO)(2), (3) INSIGHT-004
			Melanoma (IO – IO) (1) TACTI-mel			§		US$4.5 billion
			Solid Tumors (In situ Imm	unization)(2) INSIGHT
			Solid Tumors (Cancer Vacc YNP01 and YCP02	ine)(4a)
			Metastatic Breast Cancer (C	hemo – IO)(4b)			Chinese Rights	US$2.3 billion
						~~§~~
		Efti	COVID-19 disease (Monoth EAT-COVID	erapy)(7)		~~§~~	Global Rights(8)
		IMP761 (Agonist AB)				~~§~~	Global Rights	US$149.4 billion (2025)
9 9	Notes
	* (1) I (2) I (3) I (4)

Immutep Out-Licensed Immunotherapy Pipeline*

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Commercial
Program Preclinical Phase I Phase II Late Stage [(1)] Updates
Rights/Partners
Solid Tumors + Blood Cancer (IO-IO Combo)
Triple Negative Breast Cancer (Chemo-IO Combo)
Novartis currently has five
Global Rights clinical trials ongoing for
LAG525
Melanoma (IO-IO-Small Molecule Combo) LAG525 in multiple cancer
(Antagonist AB)
§ indications for over 1,000
patients [(4)]
Solid Tumors (IO-IO Combo)
Triple Negative Breast Cancer
(Chemo-IO-Small Molecule Combo)
Ulcerative ColitisUlcerative Colitis [(6)]
Two successful Phase I
Global Rights
studies, but the Phase II
GSK‘781
Healthy Japanese and Caucasian Subjects [(2)]
clinical study in up to 242
(Depleting AB)
§ ulcerative colitis patients was
discontinued.
Psoriasis [(3)]
Oncology
Autoimmune
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Notes

10 * Information in pipeline chart current as at May 2021 10 (1) Late stage refers to Phase IIb clinical trials or more clinically advanced clinical trials (2) Reflects completed Phase I study in healthy volunteers

(4)

(5)

https://clinicaltrials.gov/ct2/results?cond=&term=LAG525&cntry=&state=&city=&dist= https://clinicaltrials.gov/ct2/results?cond=&term=GSK2831781&cntry=&state=&city=&dist= and https://www.gsk.com/media/5957/q1-2020-results-slides.pdf Discontinued in Jan 2021

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Eftilagimod Alpha (efti or IMP321)

Efti: an Innovative LAG-3 IO Product Candidate

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• ➢ the only MHC II agonist (APC activator) product candidate currently in clinical development

• ➢ synergistic with other therapeutic agents and modalities e.g. IO agents or chemotherapy

“PUSHING THE ACCELERATOR ON IMMUNE RESPONSES”

“RELEASING THE BRAKE ON THE T CELL”

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Efti is an MHC II agonist

LAG-3 antagonist (or LAG-3 blocking) antibodies:

APC activator

• boosts and sustains cytotoxic T cell responses

• activates multiple immune cell subsets

Immune checkpoint inhibitor

• increases cytotoxicity of pre-existing CD8 T cell response

Notes:

12

• APC: antigen presenting cell

Efti: Potential Pipeline in a Product

Hi h intrinsic value g

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Unique APC activator (MHC II Agonist)

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Effective APC activation leads to immune activation (e.g. CD8 T cells) as shown by ex vivo and in vivo experiments, and in clinical studies

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Pipeline in a product - not limited to a select number of oncology indications, target expressions or treatment lines

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Potentially low costs of goods

Route of admin: subcutaneous Dose: 30 mg every 2 weeks*

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Efti’s safety profile enables it to be used in various combination settings

• • can be extended to every 3 weeks after 6 months

13

Boosting APCs with efti to create stronger adaptive immunity against the tumor

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Promising Efficacy & Safety

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100 Part C - 2 [nd] line HNSCC Stage 1 & 2 Best response:
75 iUPD/iCPDiSD
50 iPRiCR
25
0 PD-L1 CPS
-25
-50
-75 n = 23
-100 * cut-off 8-Oct 2020; ** LN as target lesion; *** 5 pts not evaluable; * target lesiondecrease at PD due to NL
84 % NE 100 % 1 % 2 % 70 % 50 % 40 % 75 % 25 % NY 2 % 85 %
0 % 11 % NY NE 28 % NE 0 % 41 % 1 % 0 %
Best % change from baseline
*
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Notes:

14

• APC: antigen presenting cell

Eftilagimod Alpha

Leader in it´s Class of Oncology Products

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Efti:
Interleukins
(IL2; IL15…)
•
Adenovirus No direct competition in
Interferons •
Efti
Herpes v. Mechanism of Action.
(IFN-a…)
•
CD40 Reoviruses
• TLRs Coxsackie v • No other MHC-II agonist under
•
STING
development.
•
Yescarta
•
IP protected until 2036.
•
Tecartus
•
a-CD22
•
• • Proven in randomized, placebo-
Kymriah a-CD47
• a-VEGF controlled setting.
•
a-HER2
•
Excellent safety profile.
• •
a-PD-(L)1 Low cost of goods.
•
a-CTLA-4
•
a-LAG-3 Efti is very well positioned
•
a-TIGIT in the field
•
Antigen
• Whole Cell
• Dendr. Cell
• DNA
•
a-idiotype
15
…
…
……
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Efti + Chemo Combination: Exciting interim OS results announced in December 2020

Chemothera py

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• Relatively high response rates

• But not very durable

• Reduced QoL with numerous severe side effects

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ORR Post treatment Quality of
protection Life
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How can we boost / prolong this chemotherapy-induced response with minimal additional side effects?

Activating antigen presenting cells with soluble LAG-3 via MHC II

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ORR Post treatment Quality of
protection Life
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Efti: AIPAC (Phase IIb) design

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AIPAC: Active Immunotherapy PAClitaxel in HER2[-] / HR[+] metastatic breast cancer (MBC)

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Fact sheet

Primary endpoint[(] *[)] (presented Mar. 2020) included:

• ✓ Conducted in 7 EU countries

• Assessment of Progression-Free Survival (PFS)

• ✓ Local and blinded independent central read

Secondary endpoints[(] *[)] (presented Dec. 2020) included:

• ✓ Last Patient In enrolled Jun. 2019

• Overall Survival (OS)

• ✓ Primary analysis PFS (immature OS) Mar. 2020

• Safety and tolerability

• Overall Response Rate (ORR) and other efficacy parameters

• Biomarker and Immune Monitoring

• ✓ Follow-up 1 analysis OS Sep. 2020 (SABCS Dec. 2020) – ~60% OS events

• ❖ 2[nd] OS follow-up analysis planned H2 2021

Notes:

• No hypothesis testing ORR – overall response rate, DCR – disease control rate, PFS – progression free survival, OS – overall survival, QoL – Quality of life

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AIPAC Phase IIb Clinical Results

Overall Survival – FU1 (60% events; cut-off: Sep. 20)

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Improving trend for the overall population (IIT) as data matures Currently 2.7 months difference in median OS

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Post-study treatment

was similar with 80.7% (efti) and 83.9% (placebo) receiving any post study systemic anticancer therapy. Vast majority received chemotherapy : 64.0% (efti) vs. 69.6% (placebo)

Prior CDK 4/6

have negative impact on OS in placebo group (median reduced from 20.0 to 14.9 months), but not in the efti group (median OS 20.9 vs. 20.4 months)

CDK4/6 are now standard, and most patients will have received it in future studies / real world → favorably for efti

Quality of Life (QLQ-C30)

Significant deterioration of overall QoL in the placebo group at week 25, which was not observed in the efti group

Very important for reimbursement → favorably for efti

19

AIPAC Phase IIb Clinical Results

Subgroup 1: < 65 years – PFS / OS / ORR

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Clinically meaningful absolute and relative improvement for all efficacy parameters, significance for OS ESMO scale of magnitude* = level 4 (makes reimbursement very likely)

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Patients with age < 65 yrs. Patients with age < 65 yrs.
ORR
- PFS - - OS -
50%
46%
45%
40%
38%
35%
30%
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+7.1 months median OS

Notes:

20

• used for reimbursement in Europe: https://www.esmo.org/guidelines/esmo-mcbs/scale-evaluation-forms-v1.0-v1.1

AIPAC Phase IIb Clinical Results

Subgroup 2: Low Monocytes – PFS / OS / ORR

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Clinically meaningful, absolute and relative improvement for all efficacy parameters, significance for PFS/OS ESMO scale of magnitude* = level 4 (makes reimbursement very likely)

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Patients with low monocytes Patients with low monocytes ORR
- PFS - - OS - 50%
44%
45%
40%
35%
33%
30%
25%
20%
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+9.1 months median OS
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Notes:

21

• used for reimbursement in Europe: https://www.esmo.org/guidelines/esmo-mcbs/scale-evaluation-forms-v1.0-v1.1

AIPAC Phase IIb Clinical Results

Immune Monitoring on Fresh Blood (up to 70 patients)

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Cytotoxic CD8[+] T Cell count over time (Mean + SEM million cells/L of blood; p-value Wilcoxon)

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Number of T cells increased in efti group, especially cytotoxic CD8[+] → Proof of Principle.

Stat. significant (p=0.020) Correlation: OS and cytotoxic CD8[+] T cell count Overall survival (months)

Increased number of cytotoxic CD8[+] T Cells correlated with improved OS in the efti arm → Proof of Concept.

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AIPAC Phase IIb Clinical Results

Summar and Conclusions y

First time

an APC activator has shown meaningful increase in Overall Survival (OS) in a randomised setting

Proof of Concept

Prolonged OS in the overall population and clearly linked to pharmacodynamic effect (increase in CD8 T cells)

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Proof of Principle

Significant increase in cytotoxic T cell numbers compared to placebo

Path Forward

Regulatory (FDA and EMA) discussions are prioritised now

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Efti + anti-PD-1 Combinations

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Approximately 70-80% of patients do not respond to immune check point therapy, e.g.: anti-PD-1 monotherapy.[1]

Activating antigen presenting cells with soluble LAG-3 via MHC II

How do we improve the immune response?

Notes : 2 ~~5~~ 1 See for example Callahan at al Front. Oncol. (2015) 4:385 and Gauci at al Clin Cancer Res. (2019) Feb 1;25(3):946-956.

APC activator – ICI combinations

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Three types of patients

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H
O
T
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T E P I D

C

O

L

D

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IFN
g
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Inflamed responder

Likely responds to Immune Checkpoint Inhibition e.g.: anti-PD-1

• Considerable immune cell infiltration e.g.: CD8+ Tc; Macrophages

• High levels of IFN-g produced → inducing high PD-L1 expression on tumor cells

Inflamed non-responder

Due to low level of TH1

• Some infiltrates in the tumor margins but no response.

(IFN-g) driven T-cell activation → unlikely to respond to ICI treatment

• Medium levels of IFN-g produced → inducing low PD-L1 expression on tumor cells

Non-inflamed non-responder

Due to low numbers of

• Minimal to no immune cell infiltration on the tumor margins.

• on the tumor margins. infiltrating T-cells →

• • Low levels of IFN-g produced → unlikely to respond to ICI no induction of PD-L1 expression on treatment tumor cells

26

Key Clinical Trials

TACTI-002 (Phase II) design & status

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TACTI-002: Two ACTive Immunotherapeutics in NSCLC and HNSCC

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UNSELECTED FOR PD-L1
PART A:
S
1 [ST] LINE MET. NSCLC
C
R
PART B: COMBINED
E
2 [ND] LINE MET. NSCLC, IMMUNOTHERAPY
E
PEMBROLIZUMAB + IMP321 FOR 12
N REFRACTORY TO PD-1/PD-L1 MONTHS + 12 MONTHS
TARGETING THERAPY PEMBROLIZUMAB MONO
I
N
PART C:
G Status Report
2 [ND] LINE MET. HNSCC AFTER
PLATINUM THERAPY ✓ Fully approved in all countries
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In collaboration with

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ORR, PFS, OS, PK, biomarker, safety and tolerability

Sites in Europe / US / Australia

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• ✓ Up to 183 patients in three indications

30 mg efti (IMP321) s.c. Treatment 200 mg pembrolizumab (Keytruda[] ) i.v.

• ✓ Part A (N=36) completed; extension (N=74 recruiting)

• ✓ Part C (N=39) completed

Next :

• ✓ Part B (N=36); stage 2 recruitment ongoing

New data at ASCO in June 2021

Notes:

27

ORR – overall response rate, DCR – disease control rate, PFS – progression free survival, OS – overall survival, QoL – Quality of life

TACTI-002 Results[(1)]

1[st] line NSCLC (Part A)

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g
Best response:
120
iUPD/iCPD
100
iSD
60 iPR
iCR
40
20
0
-20
-40
-60
-80
cut-off 8-Oct 2020; n= 33
-100
0 9 18 27 36 45 54 63 72 81
weeks
% change compared to baseline
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• iORR of 36.1% [95% CI 20.8-53.8]

• 2 complete responses

• 22/36 (61%) with target lesion decrease

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Presented at
stage 1 & 2
Best response:
100
iUPD/iCPD
75 iSD
iPR
50
iCR
25
PD-L1 TPS
0
-25
-50
-75
* cut-off 08-Oct 2020; n=33; ** - LN as target lesion
-100
not yet 70 % 50 % 15 % 3 % 15 % 80 % 0% 50% 10% 1% 10% 100% 0% 75% 10% 50% 90 % 90 % 75 % 100% 0%
25% 0 % 1 % not yet 40 % 0 % 0 % 0 % NE 50 % 35 %
best % change from baseline
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• Responses in all PD-L1 subgroups:

• ORR in < 50%: 31.6% (6/19)

• ORR in ≥ 1%: 44% (11/25)

• At data cut-off, 11 pts. still under therapy

Notes:

28

(1) Preliminary data, cut-off 15 Oct 2020

TACTI-002 Results[(1)]

1[st] line NSCLC (Part A) - Benchmarking

	PD-L1 (TPS)	Pembro alone (KN042/ KN001)**	TACTI-002
ORR	Regardless_(with PD- _L1 results)	17-20%	41%*(36% regardless if PD-L1 available)
	>= 50%	39.5%	54%*
	>= 1%	27.3%	44%*
	1-49%	~17%	33%*
	< 50%	14-19%	32%*

• • only patients evaluated where PD-L1 results available (32 out of 36); ** Data for pembro derived from KN042 and KN001[(2)(3)]

• Most of pembro responses come from 50%+ and especially 90%+ TPS[(4)]

• Highest unmet medical need in < 50% TPS group → efti addresses these needs.

• TIGIT does not → effects predominantly in ≥50% groups

Efti plus pembro warrants further clinical development in 1[st] line NSCLC especially considering the excellent safety profile

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Data for pembro derived from KN042 and KN001[(2)(3) ] and ORR in PD-L1 TPS <1% was taken from doi:10.1093/annonc/mdx076 and used to calculate ORR for TPS <50 for pembro mono. TACTI-002 data cut off 08. Oct. 2020.

Notes:

(1) Preliminary data, cut-off 08 Oct 2020 for TACTI-002 (2) KEYNOTE-042: TSK Mok et al, The Lancet 2019, http://dx.doi.org/10.1016/S0140-6736(18)32409-7 (3) KEYNOTE-001: NB Leighl et al, The Lancet 2019, http://dx.doi.org/10.1016/S2213-2600(18)30500-9

29

TACTI-002 Results[(1)]

2[nd] line HNSCC (Part C)

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----- Start of picture text -----

Presented at
Part C - 2nd line HNSCC
Stage 1&2
100
cut-off 8-Oct 2020, n=23 Best response:
80
iUPD/iCPD
60 iSD
iPR
40
iCR
20
0
-20
-40
-60
-80
-100
0 9 18 27 36 45 54 63 72
weeks
% change compared to start of therapy
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➢ All patients (except one) with response ongoing

• ➢ PD-L1 all comer trial → responses in PD-L1 low expressors

Notes:

30

(1) Preliminary data, cut-off 15 Oct 2020

TACTI-002 Results[(1)]

2[nd] line HNSCC (Part C) – Benchmarking

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PD-L1 (CPS) Pembro alone TACTI-002
17.3% 50%
≥1
2% CR 16.7% CR
ORR
42.9%
Regardless
14.6% (35.7% regardless if
(with PD-L1 results)
PD-L1 available)
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• • only patients evaluated where PD-L1 results available (21 out of 28); ** Data for pembro derived from KN040[(2)]

• ORR of pembro mono generally low → increase to 22% (≥ 20 CPS) and 28% (≥ 50 CPS)[(4)]

• Duration of response drops dramatically if you add chemo[(5) ] – not the case with efti

• ORR is clearly higher with high rates of CRs; duration of response very promising (only 1 pt. with PR discontinued in TACTI-002 so far)

Efti plus pembro warrants late–stage clinical development in HNSCC especially considering the excellent safety profile

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Trial P015 Part C - Historical comparison of ORRs and CRs in metastatic HNSCC for patients who has a PD-L1 CPS of ≥1. ORR for Pembrolizumab monotherapy was taken from KEYNOTE-040.

Notes:

(1) Preliminary data, cut-off 08 Oct 2020 (2) Keynote-040 results: available from https://www.esmo.org/newsroom/press-office/KEYNOTE-040-Evaluates-Pembrolizumab-in-Head-and-Neck-Cancer (3) RL Ferris et al.: Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med 2016;375:1856-67.

(4) E Cohen et al; Annals of Oncology 2019; doi:10.1093/annonc/mdz252 (5) KN-048: The Lancet, 2019; https://doi.org/10.1016/S0140-6736(19)32591-7

31

TACTI-002 Results[(1)]

2[nd] line NSCLC (Part B) - Benchmarking

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OS - Stage 1 - Part B - NSCLC

Presented at

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100
50
0
0 6 12 18
Probability of Survival
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• All patients included in this trial had progressed on 1[st ] line therapy containing PD-1/PD-L1, confirmed by 2 consecutive scans.

• 85% of patients have PD-L1 expression level < 50%

Encouraging OS with 12 months : Comparison[(2)]

• Docetaxel mOS: 6 months

• ~24% alive at 12 months

months

• 1 confirmed PR and DCR of 35%

• 72% alive at 6.3 months → encouraging although data immature beyond 6 months

• 50+% alive at 12 months

• At data cut-off, 3 patients still under therapy

Notes:

(1) Preliminary data, cut-off 8[th] Oct 2020

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(2) CheckMate-017: DOI: 10.1056/NEJMoa1504627; N Engl J Med 2015; 373:123-135

Efti: INSIGHT-004 Trial in Solid Tumours

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INSIGHT-004 is a dose escalation study evaluating efti in combination with Bavencio ® (avelumab). Conducted as the 4[th] arm of the INSIGHT trial.

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In collaboration with

Key Results in patients with mostly cancers of the gastrointestinal tract :

• No dose limiting toxicity

• 5/12 (41.6%) patients with partial responses

Data presented at: ESMO 2020

Next : Final data expected to be presented at ASCO in June 2021

I.K.F.

Encouraging single patient cases in cancers that don’t usually benefit from immunotherapy. Only 5% of patients usually benefit.[(1)]

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Phase I

Open label trial

12 Patients: 2 cohorts of 6 patients each

6 months

Combination treatment, then 6 months avelumab monotherapy

One site Germany

Notes: Data cut-off: 12 June 2020. (1) J Tintelnot, A Stein: Immunotherapy in colorectal cancer: Available clinical evidence, challenges and novel approaches. World J Gastroenterol 2019 August 7; 25(29): 3920-3928

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TACTI-003 Trial in 1[st] line HNSCC Current Desi n + Status g

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----- Start of picture text -----

TREATMENT A
S
Pembrolizumab + Efti
C COHORT A RANDOMIZATION 1:1
R
PD-L1 CPS ≥1 TREATMENT B ORR, PFS, OS, PK,
E
biomarker, safety and
E Pembrolizumab alone
tolerability
N
I
N
G COHORT B TREATMENT
PD-L1 CPS <1 Pembrolizumab + Efti
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Design:

• Randomised study with ORR as primary endpoint

In collaboration with

• Sites worldwide (AU, US, Europe)

• Approx. 154 pts: either to be randomized to have sufficient pts. in each group or in an experimental arm

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Status:

• Advanced planning & study start up expected in mid 2021

• Fast Track designation granted by FDA in April 2021

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Efti: Current Strategic Potential & Plans

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----- Start of picture text -----

Efti is the ideal candidate to combine with
✓ chemo and ✓ PD-1/PD-L1 antagonists
Chemotherapy Eftilagimod PD-1 / PD-L1
Alpha
Pembrolizumab
Taxanes
Nivolumab
Huge
Potential
Other Chemo
Avelumab
…
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Efti’s current data base includes[(1)] :

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Up to 219 patients in anti-PD-(L)1 combinations

272 patients

in chemo-immuno combination

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Safety & efficacy

Good safety & encouraging efficacy data in NSCLC, HNSCC, melanoma and MBC

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Big pharma

A variety of development options with big pharma support

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Other Efti Partnerships

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• EOC, an Eddingpharm spin-off holding the Chinese rights for efti, Phase I study in MBC ongoing with a Phase II trial in preparation

• Milestone and royalty bearing partnership

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• Spin off from NEC, Japan: aims to develop cancer drugs discovered by artificial intelligence → mainly cancer vaccines

• Clinical Trial Collaboration (up to US$5 million for Immutep); Phase I completed

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• Strategic supply partnership for the manufacture of efti

• Through WuXi, Immutep was the first company to use a Chinese manufactured biologic in a European clinical trial

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Out-Licensed Immunotherapy Pipeline

Ieramilimab (LAG525) for Cancer

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• Novartis holds an exclusive WW licence to develop and commercialise Ieramilimab (which is derived from Immutep’s antagonist antibody known as IMP701)

• 1st and 2nd milestone payments received by Immutep in August 2015 (undisclosed) and August 2017 (US$1 million)

• In 2018 Novartis cancelled 90 other R&D programs but continued to invest heavily in progressing the development of LAG525[(1)]

• Novartis currently has five clinical trials ongoing for Ieramilimab in multiple cancer indications for over 1,000 patients[(2)]

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• Ieramilimab is an anti-LAG-3 mAb that blocks LAG-3-mediated immune down-regulation

• LAG-3 is a prime target for immune checkpoint blockade as it is readily expressed at a high level in many human tumors

Notes

(1) https://www.fiercebiotech.com/biotech/novartis-dumps-20-programs-following-pipeline-review (2) Details on all ongoing trials of LAG525 being conducted by Novartis: https://www.clinicaltrials.gov/ct2/results?cond=&term=novartis+lag525&cntry=&state=&city=&dist=

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GSK’781 (IMP731) for Autoimmune Diseases

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• GSK holds an exclusive WW licence to develop and commercialise GSK’781 (which is derived from Immutep’s depleting antibody known as IMP731)

• Up to ₤64 million in upfront payments and milestones, plus royalties

• GSK portfolio review in 2017 -> GSK’781 continued despite cancellation of 13 clinical and 20 preclinical programs[(1)]

• March 2018: Phase I trial in psoriasis completed in 67 subjects/patients[(2)]

• September 2019: 1[st] patient dosed in Phase II trial in ulcerative colitis in 242 patients triggered a £4 million (~US$5.0 million) milestone payment to Immutep[(2)]

• Phase I clinical study completed, evaluating GSK’781 in 36 healthy Japanese and Caucasian subjects, PK/PD study[(2)]

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• Phase II in Ulcerative Colitis discontinued in January 2021

GSK’s investigational product, GSK2831781, which is derived from IMP731 antibody, aims to kill the few activated LAG-3[+] T cells that are auto-reactive in autoimmune disease leading to long term disease control without generalized immune suppression

Notes

39

(1) https://www.biopharmadive.com/news/glaxosmithkline-gsk-rd-pipeline-restructuring-cut-q2-earnings/447924/ (2) For additional information refer https://www.clinicaltrials.gov/ct2/results?cond=&term=GSK2831781&cntry=&state=&city=&dist=

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IMP761 - Autoimmune Diseases -

Broad potential in targeting auto-reactive memory T cells with IMP761

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THE PRESENT: FIGHTING THE SYMPTOMS

: Treating general inflammation corticoids, methotrexate, anti-TNF-α, -IL-6, -IL-17, -IL-23 mAbs

THE FUTURE: FIGHTING THE CAUSE : Treating the disease process silencing the few autoimmune memory T cells accumulating at the disease site with IMP761

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POTENTIAL GAME CHANGER IN AUTOIMMUNE DISEASES ($149.4 billion market size by 2025)[1]

Notes

41 (1) Source: KBV Research July 2019

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Other Partnerships

Collaboration with LabCorp

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• Licence and Collaboration Agreement for immunooncology products or services (entered in Oct 2020)

• Development of lab tests that may help oncologists select the right therapeutic options for their patients

• Upfront and potential commercial milestone and service-related payments to Immutep

Laboratory Corporation of America Holdings (LabCorp) is a leading global life sciences company focused on guiding patient care that provides diagnostic, drug development and technology-enabled solutions for more than 160 million patient encounters per year.

• Immutep selected for its LAG-3 expertise

Enables Immutep to enter the immuno-oncology diagnostics market through its technology and LAG-3 expertise

43

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Corporate Snapshot & Outlook

Corporate Snapshot

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IMM (ASX) Ticker symbols IMMP (NASDAQ) Securities on issue[(1)] 672.4 million ordinary shares (as at 10 May 2021) Cash & Cash equivalents ~A$51.7 million (US$39.3 million) (as at 31 March 2021) Market Cap[(2)] A$302.6 million (US$237.7 million) (as at 10 May 2021)

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Notes:

• (1) Currently ~36% of the ordinary shares listed on ASX are represented by ADSs listed on NASDAQ where 1 ADS represents 10 ordinary shares. For a detailed summary of securities on issue refer to latest Appendix 2A released on ASX.

• (2) Market capitalization based on ASX share price and basic ordinary shares outstanding.

• NB: US equivalent of amounts above are based on foreign exchange rate for AUD/USD of 0.7856 for market capitalization, and the US cash & cash equivalents amount was

• calculated using FX rate of 0.7602 as at 31 March 2021.

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2020 & 2021 News Flow*

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2020
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• ✓ AIPAC – PFS, ORR and OS delivered

• ✓ US IND for MBC

• ✓ TACTI-002 – recruitment & data delivered e.g. at ASCO, EMSO & SITC for

• ✓1[st] line NSCLC

• ✓2[nd] line NSCLC

• ✓2[nd] line HNSCC

• ✓ Support of global COVID efforts (Phase II)

• ✓ New partnerships : LabCorp

• ✓ Progress from IMP761

• ✓ Expansion of IP portfolio

• ✓ Strong financial position

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2021
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• ❑ Final data from AIPAC : 2[nd] OS follow up

• ❑ Data from TACTI-002 & final data from INSIGHT-004 at ASCO

• ❑ Recruitment & first data from TACTI-002 Part A extension

• ❑ Start & ongoing recruitment of new trial in 1st line HNSCC (TACTI-003)

• ❑ Ongoing regulatory engagement

• ❑ Updates from IMP761

• ❑ Updates from partnered programs (e.g. GSK, Novartis, EAT COVID, CYTLIMIC and EOC Pharma)

• ❑ Potential new partnerships and expansion of existing programs

• ✓ Validation of LAG-3/MHC-II interaction through readout of BMS’s Phase III data for relatlimab + nivo combination

Notes:

46

*The actual timing of future data readouts may differ from expected timing shown above. These dates are provided on a calendar year basis.

Summary

Global leadership position in LAG-3 with four LAG-3 related product candidates in immuno-oncology and autoimmune disease

Compelling clinical data from efti & strong rationale to combine with multiple FDA approved treatments

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Multiple active clinical trials (including partnered candidates), with further significant data read-outs in 2021

Established collaborations with e.g. Merck (MSD), Pfizer / Merck KGaA, Novartis and GSK

47

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Thank You