IMMUTEP LIMITED — Investor Presentation 2018

May 29, 2018

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New Data from Ongoing Melanoma Study and Clinical Development Strategy Update

Webcast - 29[th] / 30[th] May 2018

(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.

Additionally, the INSIGHT investigator sponsored clinical trial described in this presentation is controlled by the lead investigator and therefore Immutep has no control over this clinical trial. 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.

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LAG-3 Overview

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Evolution of Checkpoint Therapies

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LAG-3 has the potential to be the next meaningful checkpoint target…

Timeline of Immune Checkpoint Discovery

Evolution of Immuno-Oncology Therapies

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Opdivo/ anti-LAG-3
Combination [(1)]
Opdivo/ Yervoy
combination
Yervoy
Keytruda/ chemo
Keytruda
combination
2011 1213 1415 1617 1819 2020
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• Existing immuno-oncology therapies are CTLA-4, PD-1 and PD-L1 antagonists and are approved for many disease indications

• However, only 15 - 40% of solid tumors in patients respond to monotherapy

• Immuno-oncology market will be worth approximately US$14 billion in 2019, rising to US$34 billion by 2024, with checkpoint therapies accounting for most of the market[(2)]

Notes:

• (1) Expected timing, actual results may differ (BMS ASCO 2017 Investor Presentation)

(2) Global Data, Immuno-Oncology Strategic Insight: Multi-Indication and Market Size Analysis (May 2016)

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LAG-3 Therapeutic Landscape Overview

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Immutep is the leader in developing LAG-3 modulating therapeutics

Indicates one product; size indicates stage of development, green = product either developed by Immutep or under license from Immutep

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Indicates No. of patients on trials

Sources: GlobalData, company websites, clinical trials.gov, and sec.gov

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Information as of April 23, 2018, includes also trials which are only listed as planned, includes also trials where the company may not be the sponsor

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eftilagimod alpha (efti, IMP321)

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Eftilagimod alpha (IMP321)

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Efti is a soluble recombinant fusion protein consisting of the Fc portion of a human antibody and the four extracellular domains of LAG-3

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VL
VH D4 D3 D2 D1
CL
CH1 Soluble LAG-3
Hinge
CH2
MHC II binding site
CH3
D1
IMP321
Human IgG1
“LAG-3Ig” D2
D3
D4
Hinge
CH2
CH3
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• Dimeric, very stable, high affinity for DC

• Antigen presenting cell (APC) activator

• Unique mechanism of action and potentially first-in-class

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Efti - Innovative LAG-3 IO Product Candidate

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• The only APC targeting LAG-3 product currently in clinical development

• A unique approach (“turning cold tumors into hot tumors” with LAG-3)

• Synergistic with other IO agents

“PUSHING THE ACCELERATOR ON IMMUNE RESPONSES”

“RELEASING THE BRAKE ON THE T CELL”

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Efti, an MHC II agonist (eftilagimod alpha, IMP321) :

LAG-3 antagonist antibodies:

APC activator

• Boost and sustain the CD8[+] T cell responses

• Activate multiple immune cell subsets

immune checkpoint inhibitor

• increase cytotoxicity of the pre-existing CD8 T cell response

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Efti - Clinical Development / Description

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Notes

• (1) Expected timing of data readouts and actual results and timing may differ

• (2) In combination with KEYTRUDA® (pembrolizumab); clinical trial is currently planned and not yet active

• (3) INSIGHT Investigator Initiated Trial (IST) is controlled by lead investigator; Immutep is not the sponsor, but supplies IMP321

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Efti (IMP321) TACTI-mel Results (as of 9[th] May 2018 )

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New Rationale for Combining efti (IMP321) with PD-1 Antagonists (pembrolizumab)

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Problem : Low monocyte numbers at baseline leads to poor efficacy of anti-PD-1 therapy

Solution : efti (IMP321) increases monocyte numbers in cancer patients

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1.00
0.75
Classical monocytes > 19 %
0.50
Classical monocytes < 19 %
0.25
0.00
N=51 Time (months)
Overall Survival
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Source: Krieg et al., Nat. Med. 24, 2018.

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N=15 Source: AIPAC stage 1
Classical Monocytes %
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Monocytes are important for response and survival to pembrolizumab  efti (IMP321) increases monocytes sustainably above threshold of 19 %  response to pembrolizumab more likely

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Efti (IMP321) in Melanoma TACTI-mel (IO combination) – Trial Design

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TACTI-mel = Two ACTive Immunotherapeutics in melanoma

Recommended Phase I, multicenter, 24 patients, Efti (IMP321) + Phase II dose, open label, 4 cohorts of 6 patients anti-PD-1 (Keytruda[] ) safety and dose escalation tolerability

Primary Objective	Recommended dose for Phase II with efti (IMP321) + pembrolizumab Safety + tolerability
Other Objectives	PK and PD of IMP321, response rate, time to next treatment, PFS

• Part A: efti (IMP321) at 1, 6 and 30 mg s.c. every 2 weeks starting with cycle 5 of pembrolizumab

• Status: recruitment completed; interim results on next slides

• Part B: efti (IMP321) at 30 mg s.c. every 2 weeks starting with cycle 1 of pembrolizumab

7 sites in Australia

• Status: 3 pts enrolled w/o DLTs

• Pembrolizumab (Keytruda) 2 mg/kg every 3 weeks i.v. part A and B

preliminary data, status 9th May 2018

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Efti (IMP321) in Melanoma TACTI-mel (IO combination) – Details Part A

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Study Scheme Part A:

irRC…Immune-Related Response Criteria, PFS- progression free survival, FU – follow-up

Patient population Part A:

• Patients with unresectable or metastatic melanoma with asymptomatic progression or suboptimal response after 3 cycles of pembrolizumab

preliminary data, status 9th May 2018

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Efti (IMP321) in Melanoma TACTI-mel (IO combination) – Results after Start of Combo (1)

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Baseline Characteristics	N = 18 (%)
Elevated LDH	7 (39%)
Metastasis stage M1c	15 (83 %)
Pre-treated with BRAF/MEK/ipilimumab	4 (22 %)
irPD/irSD to pembro after 3 cycles	12 (67 %)

Best Overall Response acc. to irRC	N = 18 (%)
irCR	1 (6 %)
irPR#	5 (28 %)#
irSD	6 (33 %)
irPD	6 (33 %)
Best overall response rate (ORR)	6 (33 %)
Patients with tumor shrinkage	9 (50 %)
Disease control rate	12 (66 %)

- incl. 1 pt with complete disappearance of all target lesions; CR acc. to RECIST 1.1

Waterfall Plot* (starting after 4 cycles of pembrolizumab)

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* - acc to irRC

• Patients very late stage of disease (M1c, elevated LDH)

• Majority not responding to pembrolizumab

• Tumor shrinkage in 50 % of these patients incl. 2 pts

• with complete disappearance of all target lesions

preliminary data, status 9th May 2018

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Efti (IMP321) in Melanoma TACTI-mel (IO combination) – Results after Start of Combo (2)

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Spiderplot Cohort 1-3 – May 2018
8 0 0
4 0 0
n = 1 8
1 0 0
durable responses
5 0
0
-5 0
-1 0 0
0 3 6 9 1 2 1 5 1 8 2 1
p re - s ta rt o f
p em bro com bo
m o n th s
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Conclusion
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• Complete responses of target lesions occurred after 11 and 18 months --> combination takes time to act

• 3 (out of 12 = 25 %) durable responses in first 2 dose levels  treatment and FU ongoing

• Treatment and follow-up of 3 patients in 3[rd] cohort (30 mg) ongoing

• • acc to irRC

preliminary data, status 9th May 2018

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Efti (IMP321) in Melanoma TACTI-mel (IO combination) – Single Case at 1 mg efti

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Efficacy: Metastatic Melanoma
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pre-pembro week 9 (pembro) week 25 (combo) week 37 (combo)
R R L R L R L
L
Tumor
progression
week 49 (Pembro mono) week 64 (PFS-FU)
L R L
All lesions disappeared  CR (confirmed)
patient without treatment and disease free
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preliminary data, status 9th May 2018

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Efti (IMP321) in Melanoma TACTI-mel (IO combination) – Single Case at 6 mg efti

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Sum of target lesions (TL) acc to irRC

Target lesion: chest wall; Non-target lesion: Left common iliac LN

LN
Σ TL (irRC)	100 mm²	25 mm²	25 mm²	25 mm²	0 mm²
In %	0 %	-75 %	-75 %	-75 %	-100 %
Response	NA	irPR	irPR	irPR	irPR

• Complete disappearance of target lesions  CR acc. to RECIST 1.1

• • Patient still on pembrolizumab

preliminary data, status 9th May 2018

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Efti (IMP321) in Melanoma Response Analysis Starting Cycle 1 Day 1 Pembrolizumab

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• Trial Design TACTI mel: Combination treatment of efti and pembrolizumab starts at cycle 5 in patients not responding well or progressing on pembrolizumab  difficult to compare to any historical control How does the efficacy looks from the start of pembrolizumab?

 Performed analysis of read-outs starting from cycle 1 day 1 of pembrolizumab, including the 4 cycles pembrolizumab monotherapy (“C1/D1 Analysis”)

• Overall response rate is 61% and 66% of patients are progression free 6 months after start of pembrolizumab[(1)]

• 7/12 (58 %) patients with progression (irPD) or stable disease (irSD) have a benefit by adding IMP321[(1)]

Best Overall Response acc. to irRC (C1/D1 analysis)(1)	N = 18 (%)
irCR	1 (6%)(1)
irPR#	10 (56%)(1),(2)
irSD	5 (28%)(1)
irPD	2 (11%)(1)
Best overall response rate (ORR)	11 (61%)(1)
Progression free at 6 months	12 (66%)(1)

Notes

preliminary data, status 9th May 2018

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(1) Response rates determined by C1/D1 Analysis (2) Includes 1 patient with complete disappearance of all target lesions, CR acc to RECIST1.1

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Efti (IMP321) in Melanoma Comparison to historical controls

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How does the data fit in the treatment landscape and in comparison to pembro monotherapy?

TACTI-Mel enrolled ipilimumab (ipi) naive and ipi pre-treated patients  Keynote-002 (pre-treated) and Keynote-006 (naive) used for comparison

Baseline Characteristics	Tacti-Mel (C1/D1 response analysis) Pembro 2 mg/kg N=18 in %	KN-006 (ipi naive) Pembro 10 mg/kg n=277 In %	KN-002 (ipi pre-treated) Pembro 2 mg/kg n=180 In %
Metastasis stage M1c	83%	68%	82%
ECOG 1 / 0	22% / 78%	32% / 68%	45% / 55%
irCR	6%(1)	6%(2)	2%(2)
ORR	61%(1)	33%(2)	21%(2)
Progression free at 6 months	66%(1)	46%(2)	34%(2)

61 % response rate (1, 2) and 66 % progression free at 6 months (1, 2) with the PD-1 antagonist pembrolizumab and APC activator eftilagimod alpha in very late stage melanoma

preliminary data, status 9th May 2018 Notes (1) Response rates determined by C1/D1 Analysis

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(2) TACTImel used irRC and KN-002 and KN-006 RECIStT1.1

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Efti (IMP321) – Clinical Overview Exposure and Safety

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Exposure (2) in cancer patients

• 87 cancer patients in different indications and combinations (see table)

• Subcutaneous injection every two weeks

• 52 (~60%) received 6-30 mg efti (IMP321)

	Cancer patients
Combination partner / indication	N = 87(2)
Efti(IMP321)alone / renal cell cancer	21
with paclitaxel / met. Breast cancer	48
withpembrolizumab / met. melanoma	18

Safety profile in cancer patients

• No efti (IMP321) related deaths

• In total 24 SAEs (29%) thereof 4 (5%) (possibly) related to efti[(1)]

• No MTD in any combination

• Most common adverse events: local erythema and any type of injection site reaction up to NCI-CTC grade 2

• Efti (IMP321) has very favorable safety profile up to 30 mg given s.c. every 2 weeks

• Combination with chemotherapy or PD-1 antagonists is feasible without reaching MTD

(2) Ongoing trials like randomized part of AIPAC (226 patients), IITs (n=38) or new trials (N=120) not included here

preliminary data, status 9th May 2018

Notes (1) None of them related to combination of IMP321 + pembrolizumab, all in trials in combination with paclitaxel

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Efti (IMP321) TACTI-002 - Design

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Efti (IMP321) – Clinical Development Collaboration and Supply Agreement

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• In March 2018 Immutep entered into a clinical trial collaboration and supply agreement with Merck & Co., Inc., Kenilworth, NJ, USA (known as MSD outside the United States and Canada) to evaluate the combination of efti (IMP321 ) with MSD's anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in a new Phase II clinical trial

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Efti (IMP321) – Clinical Development TACTI-002 Trial Design

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TACTI-002; a basket trial: Two ACTive Immunotherapeutics in different indications

Efti (IMP321) + Pembrolizumab Simons 2 stage; 3 (Keytruda[] ) for 12 months + max. indications; up to 120 of 12 months pembrolizumab pts monotherapy

Phase II, multinational (EU + US + AUS), open label

Primary Response rate (iRECIST) Status Report Objective • Other Safety, PFS+OS, PK, Protocol Development + IND Objectives exploratory biomarker preparation ongoing analysis • Study start expected Q.4 ‘18 Patient Part A: 1[st ] line NSCLC PD-X Population naive • First DMC meeting planned Part B: 2[nd] line NSCLC, PD-X mid ’19 refractory Part C: 2[nd] line HNSCC, PD• First data expected mid ‘19 X naive Treatment 30 mg Efti (IMP321) s.c. 200 mg Pembrolizumab i.v.

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Response rate; PFS, OS, PK, Biomarker; Safety and tolerability

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12-15 sites in Europe / US / Australia

Notes

pharmacokinetics, PD-X – any PD-1 or PDL-1 treatment

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NSCLC – non-small-cell lung cancer, HNSCC – head and neck squamous cell cancer, DMC – data monitoring comittee, PFS – progression free survival, OS – overall survival, PK –

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Efti (IMP321) Summary

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• Very favorable safety profile  no DLT/MTD reached with pembrolizumab  combination feasible and safe

• Able to induce a IFN-γ type response in patients

 Response rate of 61 % and progressions free survival rate at 6 months of 66 % in late stage mostly visceral (M1C) melanoma if combined with pembrolizumab[(1)]

• Will be investigated in combination with pembrolizumab in 3 new indications starting 2018

preliminary data, status 9th May 2018 Notes (1) Response rates determined by C1/D1 Analysis

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Thank you!

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