06 Investor Update APRIL 2021

IN THIS ISSUE:

MESSAGE FROM THE CEO VALIDATION OF LAG-3 PARTNERSHIP PROGRESS CONTINUES FINANCING INDUSTRY CONFERENCES & POSTER PRESENTATIONS OPERATIONAL SNAPSHOT OUTLOOK MARC VOIGT Message from the CEO

The last few months have certainly been a very busy period, not only for Immutep but for our whole sector. I would like to take the opportunity in our newsletter to add a bit more colour to the significance of Bristol Myers Squibb’s (BMS) first validation of a LAG-3 product, and to elaborate on our second col- laboration with MSD and our partnership with LabCorp to help develop immuno-oncology diagnostics.

From an industry perspective, March 2021 delivered the news we had all been anticipating for years: the validation of LAG-3 as the next emerging target.

This validation came in the form of BMS’s announcement that its Phase II/III trial evaluating the combination of relatlimab, an anti-LAG-3 antibody, and Opdivo, an approved anti-PD-1 blockbuster drug, in melano-ma patients had met its primary endpoint of progression-free survival (PFS). In other words, they report-ed the combination immunotherapy was helping patients.

BMS intends to release the details of the results at an industry conference soon. However, the top line results are enough to confirm the interaction between LAG-3 and MHC II (the ligand that LAG-3 naturally binds to) can be manipulated to help the body’s immune system fight (See Diagram 1).

This is a significant milestone for cancer immunotherapy. We can now expect LAG-3-related products to be featured prominently with more interest from partners and investors. LAG-3 is advancing quickly to be-come the next emerging target for immunotherapy behind PD-1 and CTLA-4.

Diagram 1. Current immunotherapy targets including PD-1 and CTLA-4, which have approved therapeu- tic products available for patients, plus LAG-3 which uniquely binds to the MHCII complex of an presenting cell.1

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1 https://www.frontiersin.org/files/Articles/402607/fimmu-09-01909-HTML/image_m/fimmu-09-01909-g001.jpg 2 MARC VOIGT Message from the CEO

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BMS’s news is especially significant for the LAG-3 industry. It represents further validation of LAG-3, an immune checkpoint that has been attracting increasing interest over the years, as can be seen by the exponentially increasing rate of publications shown at Diagram 2.

Immutep’s CSO and CMO, Prof Frédéric Triebel, discovered LAG-3 in 1990 and has spent the last 30 years working in the field. In the interview below entitled “Validation of LAG-3”, Prof Triebel reflects on his journey with LAG-3.

Immutep remains the only LAG-3 pure-play with more programs around LAG-3 than anyone else in the field, including big pharma.

Within the exciting and growing LAG-3 space, Immutep continues to be the worldwide leader in devel- oping LAG-3 therapeutics. We are contributing four product candidates which are being evaluated in multiple clinical trials. No other company has such depth of pipeline or knowledge. This is one of the key reasons LabCorp partnered with us to develop LAG-3 diagnostic tests.

In addition, we have the only MHC II agonist product candidate in development, known as efti. Efti is an immune booster that has the versatility to be paired with PD-1 (or PD-L1) antagonists in combination therapies. Notably, efti has a very different and unique mode of action from anti-LAG-3 products such as relatlimab or leramilimab (LAG525) and this has several advantages that broaden our opportunity (See Two Modes of Action for LAG-3 article). It also puts us in a category with no current competition (see Overview of the LAG-3 Landscape at Diagram 3), while being part of practically every field of LAG-3 related therapies i.e. with an agonist soluble LAG-3 protein and an antagonist antibody for oncology and an agonist and a depleting antibody for autoimmune diseases.

We were also happy to inform you in mid-March 2021 that Immutep had deepened our relationship with MSD through a second collaboration with them. MSD (known as Merck & Co. in the USA) is an American multinational pharmaceutical company and one of the largest pharmaceutical companies in the world.

As you can imagine, this new collaboration involved much work from our team and I would like to thank them for their steadfast commitment. We have certainly become a very effective team, having success- fully secured multiple partnerships already (see our pipeline as summarised in the Operational Snapshot section). Of course, there is always more to do on that front, and I can assure you that we always look to the future for further opportunities to build the value of Immutep!

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3 MARC VOIGT Message from the CEO

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Two Modes of Action for LAG-3

The first mechanism of action relates toantagonist LAG-3 drugs, such as relatlimab (BMS) or leramilimab (LAG525 from our licensee Novartis). These drugs are antibodies that bind to the naturally occurring LAG-3 proteins on T cells, blocking anything else from binding. When these antagonist drugs, also known as an-ti- LAG-3 drugs, are bound, the LAG-3 receptor on activated T cells can’t bind MHC II molecules expressed by antigen presenting cells (APC) such as dendritic cells. LAG-3 is an inhibitory receptor on T cells; when LAG-3 is engaged by MHC II, it down-regulates activation. Therefore, blocking the MHC II-LAG-3 interaction is analogous to releasing the brakes on the activated T cells.

Antagonists need to be given to patients at higher doses to ensure the drug can bind to all LAG-3 molecules all the time to completely block the MHC II-LAG-3 interaction. From a medical perspective, the recent BMS announcement validates the physiological importance of this MHC II-LAG-3 interaction as the simple block- ade of this interaction at the tumor site or in the draining lymph node leads to clinical benefit.

Efti, which is a soluble recombinant LAG-3 protein, is not an anti-LAG-3 therapy. It’s mode of action is as an MHC II agonist. It is an APC activator.

Agonists such as efti can be given at lower doses than antagonists, because they need to only bind to a few percent of MHC II receptors to trigger APC activation which, is the first step of pushing the accelerator on the immune system. Indeed, activated APCs like dendritic cells physiologically instruct the T cells what to do in terms of antigen specificity (they present antigenic peptides to T cells), direction of the immune response (anergy versus proliferation) or functionality (they give the CD8 T cells the “license to kill” signal, so that the latter cells become more cytotoxic).

See our Mode of Action video for further explanation of LAG-3 immunotherapy. https://www.youtube.com/watch?v=6EISCGYAGQw

4 VALIDATION OF LAG-3

Quick Glossary

Agonists are molecules that bind to a receptor and activate the receptor to produce a biological response.

Alleles are one of two, or more, forms of a giv- en gene variant.

Antagonists are a type of molecule that blocks a receptor-ligand interaction and the associated bio- logical response.

Antigen presenting cells (APCs) process and present for recognition by T cells. They give instructions and a license to kill to CD8 T cells. Prof Frederic Triebel is Immutep’s CMO/CSO and the discoverer of the LAG-3 gene. Talking Antigens are molecules on the outside of a patho- gen cell. Cancer cells have tumour antigens. to him from his home in Normandy, France, where he is in lock down, he reflects on the MHC class II are a class of Quickmajor histocom- discovery of LAG-3 and the significance of its patibility complex (MHC) molecules. recent validation after a lifetime in the pursuit of LAG-3 knowledge for the benefit of patients. T cells destroy foreign cells (including tumour cells) in the body when given instructions from an APC.

When did you first know that LAG-3 was an important protein in the body’s immune system? Back in 1988, I was working at Institut Gustave Roussy, south of Paris and cloned mRNA specifically expressed in human T cells after their activation, therefore named Lymphocyte Activation Gene-1, -2, -3. LAG-3 was first published in May 1990 and interestingly was found to be related phylogenetically to CD4, a known ligand for MHC class II (MHC II) molecules.

This was exciting because we already knew MHC II was intricately involved in many aspects of the body’s immune response. MHC II genes and molecules are related to a multitude of different diseases. For in- stance, certain MHC II alleles are strongly associated with the risk of inheriting Type I diabetes.

What was the core question that drove your research for more than 30 years? Because we understood the power of CD8 T cells to destroy tumours in animal models and the role of the

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5 VALIDATION OF LAG-3

[Continued from p. 5] question: how could we get T cells to destroy cancer cells in patients with advanced disease? I knew the answer lay in part in the interaction between MHC II and LAG-3, that is, bridging professional APCs (dendritic cells) to activated T cells.

What is special about BMS’s news? It shows us we are all “barking up the right tree” looking into the interaction between MHC II and LAG-3. It demonstrates the interaction is important in the immune system and it can be used to destroy cancer cells. In oncology, this interaction can be leveraged in two ways, via two modes of action.

What are the two different modes of action? In this MHC II/LAG-3 interaction, one can use a soluble LAG-3 protein to “push the accelerator” (an agonist action) on the MHC II molecules in order to activate APCs (and subsequently CD8 killer T cells) or one can use a blocking anti-LAG-3 antibody to stop MHC II engaging LAG-3 receptors on T cells (an antagonist action), thereby leading directly to more activated T cells.

Both modes of action can be leveraged to restore the immune system’s ability to find and fight cancer cells but probably in different patient populations. Patients with so-called “cold or tepid” tumors (the ma- jority of patients, with few activated T cells at the tumor site) need APC activation via efti to induce more T cells to recognise effectively the tumour cells while “hot” tumor patients, unfortunately the minority, with a strong natural tumour bed infiltration by activated T cells could benefit from the antagonist effect, releasing the brakes on the T cells using an anti-LAG-3 antibody. (For more detail see Two Modes of Action for LAG-3).

Were there any moments along the LAG-3 journey where you had doubts? I have always believed in LAG-3. However, there were times in the industry where it was difficult to con- vince others of LAG-3’s potential. For a long time, was the number one treatment for many , including breast cancer. The higher the dose, the more effective the chemo. The trouble was, it is very toxic and not very effective in many other indications.

Still, it was difficult to shift the paradigm. Then cancer vaccines came along. They were very hard to de- velop and there were many failures. They were safe, but they didn’t work. This made the oncology world less open to new ideas. And then from 2010 onwards, the change came gradually when oncologists used anti-CTLA-4 and anti-PD-1 antibodies in randomised clinical trials. These antibodies are not anti-cancer agents per se. CTLA-4 or PD-1 are not expressed by tumour cells. They just unleash the power of the natural pre-existing T cell responses specific for tumor antigens. The anti-cancer agents are the patient CD8 T cells themselves that could get rid of massive metastatic tumour lesions in a few weeks. In short, we moved from a small field of cancer immunotherapy experimentations with early phase clinical trials to a new full-fledged medical science, named immuno-oncology.

Have there been sacrifices, personally or professionally along the way? Absolutely! I wanted to focus completely on LAG-3, so I started Immutep with John Hawken in Septem- ber 2001. It was just after the attack on the Twin Towers in New York. It was a hard time to start a new biotech, very difficult to raise cash in Europe due to the war in Iraq.

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6 VALIDATION OF LAG-3

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I left my secure clinical job at the Institut Gustave Roussy, south of Paris, in 2002 and then quit my teach- ing job as a Professor at the Paris-Sud university in 2004 and have also been the first investor, risking the financial wellbeing of my family at that time. I burned my vessels on the beach like Agamemnon!

Now that LAG-3 has been validated, what will happen next in the LAG-3 space? We have been waiting for BMS’s results for the last three years, ever since they completed their phase II trial. We have never known the results of the earlier phase II trial, but obviously they were strong enough for BMS to decide to proceed with the phase III.

I expect there will be more news coming from BMS which has 38 trials running in different indications. We will also have a flurry of results from others in the space. It will go from being a secret with unknown materiality, to an open race to the finish line! Of course, Immutep and its many collaborators will signifi- cantly contribute to the LAG-3 related developments as well!

Where do you see LAG-3 10 years from now? There is lots of work to be done to fully appreciate the significance of the MHC II/LAG-3 interaction not only in immuno-oncology but also in autoimmunity and infection. We have a good chance of success in autoimmune diseases with IMP761 (a LAG-3 agonist antibody), and in oncology and infectious diseases with efti.

More broadly, I believe will be expanded beyond cancer and clearly defined autoim- mune diseases, into new fields. We can use the new tools we have in immuno-oncology in other thera- peutic fields where we don’t quite understand the implication of T cell aggressiveness, like arterioscle- rosis or Parkinson disease (LAG-3 clearly plays a role there) or Alzheimer’s disease. It is truly exciting!!

LAG-3 LANDSCAPE

Diagram 2. Acceleration in the LAG-3 space. Source: PubMed

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7 VALIDATION OF LAG-3

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Interest and investment in LAG-3 therapeutics has continued to accelerate over the last year. There are now more than 91 clinical trials evaluating 15 LAG-3 product candidates for more than 17,000 patients (See diagram 3).

Immutep and our collaboration partners have contributed to 22 trials for more than 2,000 patients. Apart from Immutep’s candidates, all other LAG-3 candidates shown at Diagram 3 are all anti-LAG-3 antago- nist antibodies with similar mechanisms of action being evaluated in cancer trials. Immutep’s IMP761 and IMP731 (licensed to GSK) are being developed for autoimmune diseases.

Many pharmaceutical companies have entered the space and are rapidly advancing promising product candidates, including BMS, Roche, Boehringer Ingelheim, plus our existing partners Novartis, MSD and GSK and more than 30 others. Still, Immutep has an excellent and leading position in the field! However, Immutep continues to have the only MHC II agonist in late-stage clinical development, as shown below (Diagram 3). DiagramLAG 3.- The3 Therapeutic LAG-3 therapeutic Landscape landscape. Overview

Company Program Preclinical Phase I Phase II Phase III Total Trials Patients

Eftilagimod 14 940 Alpha(5) 10 5 Agonist BMS Relatlimab 39 10,186 10 27 2 Ieramilimab 5 1,069 Validation 1 4 “demonstrate a Macrogenics Tebotelimab benefit for 6 1054 (6) 3 3 patients” Merck & Co. MK4280 5 1080 Inc. 2 3

B.I. BI754111 4 1 5 380

(1) Regeneron Fianlimab 1 1 2 769 Oncology H-L Roche RO7247669 1 1 2 575 Antagonist Incyte INCAGN02385 1 1 2 74

(2) Symphogen SYM022 3 3 223

(3) Tesaro TSR-033 2 2 75

Innovent IBI110 1 1 268

Xencor XmAb-22841 1 1 242

F-Star FS-118 1 1 80

IMP761 -- -- Agonist

(4) Autoimmune GSK2831781 AB 2 3 164 (IMP731) 1 Depleting Depleting Sources: GlobalData, Company websites, clinicaltrials.gov, and sec.gov, as of April 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 (https://www.sec.gov/Archives/edgar/data/872589/000110465919000977/a19-1325_18k.htm) 4) Includes two completed Phase I studies and one discontinued Phase 2 study (see slide 9) 2) On 3 Apr. 2020 Les Laboratoires Servier Acquires Symphogen 5) Including IITs, two planned trials (MBC trial by EOC and HNSCC trial) 3) Tesaro was acquired by and is now part of GSK (www.gsk.com/en-gb/media/press-releases/gsk-completes-acquisition-of-tesaro-an-oncology-focused- 6) RELATIVITY-047 (https://investors.bms.com/iframes/press-releases/press-release-details/2021/Bristol-Myers-Squibb-Announces-RELATIVITY-047-a-Trial- biopharmaceutical-company/ ) Evaluating-Anti-LAG-3-Antibody-Relatlimab-and-Opdivo-nivolumab-in-Patients-with-Previously-Untreated-Metastatic-or-Unresectable-Melanoma-Meets-Primary- Endpoint-of-Progression-Free-Survival/default.aspx)

Sources: GlobalData, Company websites, clinicaltrials.gov, and sec.gov, as of April 2021. The green bars above represent programs conducted by Immutep &/or its partners. Total Trials includes all active, completed &/or inac- tive trials. Patient totals are based on estimated total enrolled &/or to be enrolled. The above is 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 (https://www.sec.gov/Archives/edgar/data/872589/000110465919000977/a19-1325_18k.htm) 2 On April 3, 2020 Les Laboratoires Servier acquired Symphogen 3 Tesaro was acquired by and is now part of GSK (www.gsk.com/en-gb/media/press-releases/gsk-completes-acqui- sition-of-tesaro-an-oncology-focused-biopharmaceutical-company/) 4 Includes two completed Phase I studies and one discontinued Phase 2 study 5 Including IITs, two planned trials (MBC trial by EOC and HNSCC trial) 6 RELATIVITY-047 (https://investors.bms.com/iframes/press-releases/press-release-details/2021/Bristol-My ers-Squibb-Announces-RELATIVITY-047-a-Trial-Evaluating-Anti-LAG-3-Antibody-Relatlimab-and-Opdi vo-nivolumab-in-Patients-with-Previously-Untreated-Metastatic-or-Unresectable-Melanoma-Meets-Primary-End point-of-Progression-Free-Survival/default.aspx) 8 

PARTNERSHIP PROGRESS CONTINUES

Second Collaboration with MSD In mid-March 2021, we were delighted to deepen our relationship with MSD (Merck & Co) through a second clinical trial collaboration and supply agreement.

Called TACTI-003, the new trial evaluates efti in combination with MSD’s KEYTRUDA® () as a first line therapy in unresectable recurrent or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) patients.

This is the same combination therapy already being tested in Immutep’s ongoing Phase II TACTI-002 study (also designated KEYNOTE-798) and is delivering very promising results in second line HNSCC.

Planning for the new trial is progressing well and we expect to enroll the first patient in the study in mid-2021.

New Agreement with LabCorp In late October, we started a new collaboration with the Laboratory Corporation of America Holdings, known as LabCorp. Working with LabCorp, we will support the development of immuno-oncology prod- ucts or services. This work enables Immutep to enter the immuno-oncology diagnostics field.

Interestingly LabCorp and Bristol Myers Squibb have an abstract at AACR 2021, discussing the expres- sion of LAG-3 in different cancer types. It shows how closely the industry works together.

Our deep LAG-3 pipeline and highly experienced team reflects a significant amount of know-how in immuno-oncology, specifically related to LAG-3.

9 

FINANCING

Demonstrating strong interest and confidence in Immutep’s clinical program from existing and new high-quality investors, we completed a A$29.6 million placement in November 2020. Australian Ethical, Perennial Value Management, Regal Funds Management, Firetrail Investments and US-based, Ridge- back Capital were all leading participants in the capital raise.

In addition, in December 2020, the Company received $10.66 million from the exercise of warrants over American Depository Shares.

The proceeds will drive the ongoing development of our promising immuno-oncology and autoimmune programs. Immutep now has a strong cash runway, into calendar year 2023 and beyond several signifi- cant data read-outs.

10 INDUSTRY CONFERENCES

Immutep was pleased to announce new data from our TACTI-002 phase II clinical trial (also designated KEYNOTE-798) at the Society for Immunotherapy of Cancer (SITC) 35th Anniversary 2020 Annual Meeting in November. More mature data from the trial was accepted as a late breaker poster presenta- tion and poster walk for highly scored abstracts.

The data showed Overall Response Rates (ORR) in 1st line Non-Small Cell Lung Cancer (NSCLC) and 2nd line HNSCC had continued to be very favourable. Five patients demonstrated a Complete Response (a complete disappearance of all tumour lesions): two patients were in the 1st line NSCLC group and three patients were in the 2nd line HNSCC group. The results also demonstrated encouraging efficacy in low PD-L1 expressing patients who do not typically respond to anti-PD-1 therapy.

SITC is the world’s leading member society of medical professionals dedicated to advancing cancer immunotherapy and biological therapy.

A month later, in December 2020, Immutep presented data from our phase IIb APIAC trial in metastatic breast cancer at the San Antonio Breast Cancer Symposium (SABC). The data was selected for a spotlight presentation and showed a statistically significant survival benefit for key patient groups.

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11 INDUSTRY CONFERENCES AND POSTER PRESENTATIONS

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Specifically, a statistically significant Overall Survival (OS) benefit was seen in the efti group in pre- defined patient groups. Patients under the age of 65 years showed a +7.1 months survival benefit (median of 21.9 vs. 14.8 months, nearly 50% longer) from efti with chemotherapy, compared to chemo- therapy plus placebo (p=0.012). A +9.4 months survival benefit (median of 22.4 vs. 12.9 months, 74% longer) was seen from efti with chemotherapy for patients with a low starting monocyte count (p=0.02).

A statistically significant increase in CD8 T cells (key immune cells) was observed in patients treated with efti plus chemotherapy and this increase correlated with prolonged OS, indicating pharmacodynamic activity and proof of concept of efti’s mode of action.

In addition, a promising and improving overall trend in OS in the total population was observed, based on approximately 60% of events. A median survival benefit of +2.7 months from the efti plus chemotherapy group was reported.

The results were the first time an antigen presenting cell (APC) activator has shown an OS benefit in a randomised setting in metastatic breast cancer patients known to be insensitive to immune checkpoint inhibitor therapy. The collection of OS is data ongoing and final data is expected to be reported mid-2021.

SABC is a leading international conference focused on clinical, translational and basic research in breast cancer. It is attended by a broad international audience of academic and private researchers and physicians from over 90 countries.

Following the encouraging results presented at SITC and SABC, we have prioritised the recommence- ment of scaling up the manufacturing efti.

12 

OPERATIONAL SNAPSHOT

OPERATIONAL SNAPSHOT

OPERATIONALEftilagimod SNAP SHOT Global Rights AIPAC OPERATIONALAlpha SNAPSHOT Phase IIb (efti or IMP321) Metastatic Breast Cancer (Chemo – IO) Oncology § Eftilagimod Global Rights AIPAC EftilagimodAlpha Phase IIb Global Rights Overall(efti or Survival IMP321) (OS) dataAIPACMetastatic from the Breast AIPAC Cancer clinical (Chemo trial were– IO) presented at SABCS 2020 (see Industry Conferences for a summary of the results). Oncology Alpha Phase IIb § OverallThe c ollectionSurvival of OS (OS) data is data ongoing from and final the data AIPAC is expected clinical to be reported trial were mid-2021 presented. at SABCS 2020 (see Industry (efti or IMP321) Metastatic Breast Cancer (Chemo – IO) Oncology § ConferencesOPERATIONAL forSNAP aS HOTsummary of the results). The collection of OS data is ongoing and final data is Overall Survival (OS) data from the AIPAC clinical trial were presented at SABCS 2020 (see Industry Conferences for a summary of the results). expectedOverallThe collection Survivalto be of(OS) OSreported datadata is from ongoing mid-2021. the AIPAC and final clinical data trial is expected were presented to be reported at SABCS mid 2020-2021(see. Industry Conferences for a summary of the results). OPERATIONALEftilagimod SNAPSTACTIHOT -002 (KEYNOTE-798) Global Rights The collectionAlpha of OS dataAIPACNon is-Small ongoing-Cell and Lung final Carcinoma data is expected (IO – IO) to be reported mid-2021Phase. II Phase IIb (efti or IMP321) MetastaticHead and NeckBreast Squamous Cancer (Chemo Cell Carcinoma– IO) (IO – IO) § Oncology § Global Rights Eftilagimod Global Rights

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Oncology §

Oncology January 2021. Further interim data from TACTI-002 is expected in H1 of 2021. In September 2020, Immutep reported improving data from the INSIGHT-004 trial. 41.7% of patients showed a Partial Response to the Immutep is progressing well with plans to start the study12 in mid-2021. ImmutepcombinationIn September is progressing therapy 2020, Immutep of wellefti and with reported avelumab plans toimproving start, buildingthe data study on thefrom in previously midthe- 2021.INSIGHT reported-004 trial. result41.7% of 33% of patientsshowing showed a Partial a Response.Partial Response to the Eftilagimod Global Rights combination therapy INSIGHTof efti and-004 avelumab, building on the previously reported result of 33% showing a Partial Response. EftilagimodAlpha Phase I Global Rights

(efti or IMP321) SolidTACTI Tumors-003 (IO – IO) 12 Oncology Alpha Phase II § Eftilagimod Head and Neck Squamous Cell Carcinoma (IO – IO) Global Rights (efti or IMP321) INSIGHT-004 12 § Alpha Phase I Solid Tumors (IO – IO) Oncology In (eftiSeptember or IMP321) 2020, Immutep reported improving data from the INSIGHT-004 trial. 41.7% of patients showed a Partial Response to the Oncology § combinationImmutep is progressing therapy of wellefti and with avelumab plans to ,start buildingthe studyon the in previously mid-2021. reported result of 33% showing a Partial Response. In September 2020, Immutep reported improving data from the INSIGHT-004 trial. 41.7% of patients showed a Partial Response to the combination therapy of efti and avelumab, building on the previously reported12 result of 33% showing a Partial Response. Eftilagimod Global Rights In September 2020,INSIGHT Immutep-004 reported improving data from the INSIGHT-004 trial. 41.7% of patients Alpha Phase I showed(efti ora IMP321)Partial ResponseSolid Tumors to(IO the– IO) combination therapy12 of efti and avelumab, building on the previously

Oncology § reported result of 33% showing a Partial Response. In September 2020, Immutep reported improving data from the INSIGHT-004 trial. 41.7% of patients showed a Partial Response to the Encouragingcombination therapyearly ofanti-tumourefti and avelumab activity, building signals on the previously were observedreported result in of a33% varietyshowing of a Partial cancer Response. indications not typ- ically responsive to immunotherapy. Importantly, the 12combination of efti and avelumab continues to be safe and well tolerated. Final data is expected in 2021.

[Continued on p. 14]

13 OPERATIONAL SNAPSHOT

Encouraging early anti-tumour activity signals were observed in a variety of cancer indications not typically responsive to immunotherapy. Importantly, the combination of efti and avelumab continues to be safe and well tolerated. Final data is expected in 2021. [Continued from p. 13]

Encouraging early anti-tumour activity signals were observed in a variety of cancer indications not typically responsive to immunotherapy.

Importantly, the combination of efti and avelumab continues to be safe and well tolerated. Final data is expected in 2021. Eftilagimod Global Rights TACTI-mel Alpha PhasePhase II Melanoma (IO – IO) (efti or IMP321) Oncology Encouraging early anti-tumour activity signals were observed in a variety of cancer indications not typically responsive§ to immunotherapy. Importantly, the combination of efti and avelumab continues to be safe and well tolerated. Final data is expected in 2021. The results of Immutep’s TACTI-mel trial were featured prominently in Issue 38 of the Melanoma Research Review which is a summary of the EncouragingEftilagimod early anti-tumour activity signals were observed in a variety of cancer indications not typically responsive to immunoGlobaltherapyRights. Thelatest results research of inImmutep’s melanomaTACTI- formel TACTI-melhealth professionals. trial Healthcarewere featured professionals prominently can access the Reviewin Issue for free 38 online of the at: Melanoma Re- Alpha PhasePhase II Importantly, the combinationMelanoma of efti (IO –andIO) avelumab continues to be safe and well tolerated. Final data is expected in 2021. (efti or IMP321) searchOncology Review which is a summary of the latest research in melanoma for health professionals.§ Health- www.researchreview.com.au/au/Clinical-Area/Internal-Medicine/Medical-Oncology/Melanoma.aspx care professionals can access the Review for free online at: Eftilagimod Global Rights The results of Immutep’sTACTI TACTI-mel-mel trial were featured prominently in Issue 38 of the Melanoma Research Review which is a summary of the Alpha PhasePhase II latest research in melanomaMelanoma for health (IO – IO) professionals. Healthcare professionals can access the Review for free online at: (eftiEftilagimod or IMP321) Global Rights www.researchreview.com.au/au/Clinical-Area/Internal-Medicine/Medical-Oncology/Melanoma.aspxOncology Solid Tumors (Cancer Vaccine) § EftilagimodAlpha PhasePhasePhase II I Global Rights www.researchreview.com.au/au/Clinical(efti or IMP321) YNP01TACTI-mel and YCP02 -Area/Internal-Medicine/Medical-Oncology/Melanoma.aspx Oncology Alpha PhasePhase II § Melanoma (IO – IO) The(efti results or IMP321) of Immutep’s TACTI-mel trial were featured prominently in Issue 38 of the Melanoma Research Review which is a summary of the Oncology §

latest research in melanoma for health professionals. Healthcare professionals can access the Review for free online at: CYTLIMIC has been conducting two studies (YNP01 and YCP02) with CYT001 which is CYTLIMIC’s lead cancer vaccine. CYT001 comprises peptides Eftilagimod Global Rights designedThe results using of Immutep’s artificial intelligence TACTI-mel fromtrial werethe HSP30 featured and prominently GCP-3 proteins, in Issue plus 38 two of adjuvants,the Melanoma efti and Research Hiltonol Review (Poly-whichICLC). isUnder a summary the terms of the of www.researchreview.com.au/au/ClinicalAlpha Solid Tumors (Cancer-Area/Internal Vaccine) -Medicine/MedicalPhasePhasePhase II I -Oncology/Melanoma.aspx clinicallatest(efti researchor collaboration, IMP321) in melanoma serviceYNP01 andforand health supply YCP02 professionals. agreement s with HealthcareImmutep, professionals CYTLIMIC has can full access responsibility the Review for for the free continued online at development: of the Oncology § cancer vaccine and Immutep is eligible to receive development-based milestone payments. www.researchreview.com.au/au/Clinical-Area/Internal-Medicine/Medical-Oncology/Melanoma.aspx CYTLIMICEftilagimod has been conducting two studies (YNP01 and YCP02) with CYT001 which is CYTLIMIC’s lead cancer vaccine. CYT001 comprisesGlobal peptidesRights Solid Tumors (Cancer Vaccine) designedAlpha using artificial intelligence from the HSP30 and GCPPhasePhasePhase-3 proteins, II I plus two adjuvants, efti and Hiltonol (Poly-ICLC). Under the terms of CYTLIMIC(eftiEftilagimod or IMP321) has beenYNP01 conducting and YCP02 two studies (YNP01 and YCP02) with CYT001 which is CYTLIMIC’sChinese Rights Oncology § clinical collaboration,Metastatic service andBreast supply Cancer agreement (Chemo –sIO)with Immutep, CYTLIMIC has full responsibility for the continued developmentGlobal ofRights the lead cancerEftilagimodAlpha vaccine. CYT001 comprises peptidesPhase Idesigned using artificial intelligence from the HSP30 cancer(efti orAlpha vaccine IMP321) and ImmutepSolid Tumors is eligible (Cancer to receive Vaccine) developmentPhasePhasePhase-based II I milestone payments. (efti or IMP321) YNP01 and YCP02 § andOncology CYTLIMICGCP-3 has proteins, been conducting plus two studies adjuvants,(YNP01 and efti YCP02) and withHiltonol CYT001 (Poly-ICLC). which is CYTLIMIC’ Unders lead cancer the vaccine.terms§ CYT001of clinical comprises collab peptides- designed using artificial intelligence from the HSP30 and GCP-3 proteins, plus two adjuvants, efti and Hiltonol (Poly-ICLC). Under the terms of oration,Oncology In December service 2020, andEOC supplyPharma announced agreements its plans with to conduct Immutep, a new phase CYTLIMIC II trial of efti has in metastatic full responsibility breast cancer. This for follow the scontinuedImmutep’s Eftilagimod announcementCYTLIMICclinical collaboration, has been of encouraging conducting service and firsttwo supply OSstudies data agreement (YNP01from its and Phases with YCP02) IIbImmut study,withep, CYT001AIPAC CYTLIMIC (see which above).has is fullCYTLIMIC’ responsibilitys lead cancer for the vaccine. continued CYT001 development comprisesChinese of peptides Rights the Alpha Metastatic Breast Cancer (Chemo – IO) Phase I developmentdesignedcancer vaccine using of artificial and the Immutep intelligencecancer is eligible vaccinefrom to the receive HSP30 and development and Immutep GCP-3 proteins,-based is milestone eligibleplus two adjuvants, paymentsto receive .efti and development-based Hiltonol (Poly-ICLC). Under themilestone terms of (efti or IMP321) payments.clinical collaboration, service and supply agreements with Immutep, CYTLIMIC has full responsibility for the continued development§ of the 13 cancer vaccine and Immutep is eligible to receive development-based milestone payments.

Oncology In DecemberEftilagimod 2020, EOC Pharma announced its plans to conduct a new phase II trial of efti in metastatic breast cancer. This followChineses Immutep’s Rights announcementAlpha of encouragingMetastatic Breastfirst OS Cancer data from (Chemo its –PhaseIO) IIb Phasestudy, IAIPAC (see above). (efti or IMP321) Eftilagimod § Chinese Rights Metastatic Breast Cancer (Chemo – IO) Alpha Phase I 13 (efti or IMP321) Oncology In December 2020, EOC Pharma announced its plans to conduct a new phase II trial of efti in metastatic breast cancer.§ This follows Immutep’s announcement of encouraging first OS data from its Phase IIb study, AIPAC (see above).

Oncology In December 2020, EOC Pharma announced its plans to conduct a new phase II trial of efti in metastatic breast cancer. This follows Immutep’s In Decemberannouncement 2020, of encouraging EOC Pharmafirst OS data announced from its Phase IIb its study, plans AIPAC 13to (see conduct above). a new phase II trial of efti in metastatic breast cancer. This follows Immutep’s announcement of encouraging first OS data from its Phase IIb 13 study, AIPAC (see above).

EOC Pharma is the exclusive licensee of efti for the Chinese market. EOC Pharma is the exclusive licensee of efti for the Chinese market.

Eftilagimod Global Rights Alpha COVID-19 Phase II Disease

Infectious Infectious (efti or IMP321) §

The University Hospital Pilsen in the Czech Republic has commenced an investigator-initiated randomised phase II clinical trial evaluating efti in up to 110 hospitalised patients with COVID-19. Recruitment of patients commenced in October 2020. The University Hospital Pilsen in the Czech Republic has commenced an investigator-initiated ran- domisedThe trial phase aims to boostII clinical a patient’s trialimmune evaluating response toeftiprevent in up the to patient 110 from hospitalised developing severe patientsCOVID-19 with symptoms COVID-19.that require Recruit intensive - care and can lead to respiratory failure and death. As an antigen presenting cell (APC) activator, efti could help to control the viral load in menthospitalised of patients patients commenced by boosting T cells. in October 2020.

Initial results from the safety run in of the trial were reported in January 2020 and showed all six patients received the three planned 10 mg efti The injectionstrial aimsand were to dischargedboost a from patient’s hospital. Noimmune adverse events response were reported to prevent. An independent the patientreview of thisfrom safety developing run-in data prompt severeed the COVID-19recommendation symptoms to proceed that with require enrolment intensivefor the randomised care portionand canof the lead EAT COVID to respiratorystudy. failure and death. As an antigenInitial presenting interim efficacy cell results (APC) are expected activator, to be reported efti could before help the end to of control the year. the viral load in hospitalised patients by boosting T cells.

Global Rights IMP761 Preclinical (Agonist AB) § Autoimmune [Continued on p. 15]

14

14 OPERATIONAL SNAPSHOT

EOC Pharma is the exclusive licensee of efti for the Chinese market.

Eftilagimod Global Rights Alpha COVID-19 Phase II Disease

Infectious (efti or IMP321) § [Continued from p. 14] The University Hospital Pilsen in the Czech Republic has commenced an investigator-initiated randomised phase II clinical trial evaluating efti in up to 110 hospitalised patients with COVID-19. Recruitment of patients commenced in October 2020.

The trial aims to boost a patient’s immune response to prevent the patient from developing severe COVID-19 symptoms that require intensive Initialcare results and can leadfrom to therespiratory safety failure run and in death. of theAs trialan antigen werepresenting reported cell (APC) in January activator, efti 2020 could and help toshowed control the all viral six load patients in receivedhospitalised the patientsthree byplanned boosting T10 cells. mg efti injections and were discharged from hospital. No adverse events

wereInitial reported. results from An the independent safety run in of the review trial were of reported this safety in January run-in 2020 and datashowed promptedall six patients the received recommendation the three planned 10to mg pro efti- ceedinjections with enrolmentand were discharged for the from randomised hospital. No adverse portion events of were thereported EAT .COVID An independent study.review of this safety run-in data prompted the recommendation to proceed with enrolment for the randomised portion of the EAT COVID study. InitialInitial interim interim efficacyefficacy results results are expected are toexpected be reported to before be reported the end of the before year. the end of the year.

Global Rights IMP761 Preclinical (Agonist AB) § Autoimmune

Immutep is continuing cell line and other preclinical development activities for IMP761 in preparation for clinical trials. Immutep is continuing cell line and other preclinical development activities for IMP761 in preparation for clinicalImmutep trials.is continuing cell line and other preclinical development activities for IMP761 in preparation for clinical trials. Solid Tumors + Blood Cancer (IO-IO Combo) Phase II

Solid Tumors + Blood Cancer (IO-IO Combo) Phase II Triple Negative Breast Cancer (Chemo-IO Combo) Phase II 14 Triple Negative Breast Cancer (Chemo-IO Combo) Phase II § LAG525 (Antagonist Melanoma (IO-IO-Small Molecule Combo) Phase II § Global Rights LAG525AB) (Antagonist Melanoma (IO-IO-Small Molecule Combo) Phase II Global Rights

Oncology AB) Solid Tumors (IO-IO Combo) Phase II

Oncology Solid Tumors (IO-IO Combo) Phase II Triple Negative Breast Cancer (Chemo-IO-Small Molecule Combo) Phase I Triple Negative Breast Cancer

(Chemo-IO-Small Molecule Combo) Phase I LAG525, now called leramilimab, a humanised form of IMP701 is being evaluated by Novartis in several Phase I and/or Phase II clinical trials in combination with Novartis’ PD-1 inhibitor spartalizumab for the treatment of certain cancers. LAG525, now called leramilimab, a humanised form of IMP701 is being evaluated by Novartis in several Phase I and/or Phase II clinical trials in LAG525,combinationNovartis now has fullwith called responsibility Novartis’ leramilimab, PD-1 for inhibitor the continued spartalizumaba humanised development for the form of treatment the LAGof IMP701-3 of antibody certain isprogramcancers. being and evaluated Immutep is eligible by Novartis to receive development-in several based milestone payments and sales-based royalties. PhaseNovartis I and/or has full Phase responsibility II clinical for the continued trials indevelopment combination of the LAGwith-3 antibody Novartis’ program PD-1 and Immutepinhibitor is eligible spartalizumab to receive development- for the treatmentbased milestone of certain payments cancers. and sales -based royalties.

Novartis has full responsibility for the continued development of the LAG-3 antibody program and Immutep is eligible to receive development-based milestone payments and sales-based royalties.

15

15

[Continued on p. 16]

15 OPERATIONAL SNAPSHOT

[Continued from p. 15]

Ulcerative Colitis Phase II

GSK‘781 Global Rights Healthy Japanese and Caucasian Subjects Phase I (Depleting AB) § Autoimmune

Psoriasis Phase I

In January 2021, GSK stopped its phase II clinical trial evaluating GSK2831781 (derived from Immutep’s IMP731 antibody) in ulcerative colitis In Januarybased on the2021, assessment GSK of stopped clinical data its as partphase of a planned II clinical interim trial analysis evaluating conducted in GSK2831781 consultation with the (derived trial’s Dat afrom Review Immutep’s Committee. GSK is conducting further reporting, assessment and analyses of the efficacy and safety data and evaluating the biology to determine next steps IMP731for the antibody) GSK2831781 developmentin ulcerative program. colitis based on the assessment of clinical data as part of a planned interim analysis conducted in consultation with the trial’s Data Review Committee. GSK is conducting Importantly, Immutep’s collaboration with GSK remains in place and GSK2831781 continues to be under an exclusive license with GSK. GSK furthercontinues reporting, to have full assessment responsibility for and the development analyses of of th istheLAG efficacy-3 antibody programand safety and Immutep datais and eligible evaluating to receive development the biology-based to determinemilestone next payments steps and salesfor -thebased GSK2831781 royalties. development program. The discontinuation of the GSK trial has no impact on Immutep’s three other product candidates all of which have different mechanisms of Importantly,action, including Immutep’sefti. Immutep’s collaboration cash runway is with also unimpacted. GSK remains in place and GSK2831781 continues to be under an exclusive license with GSK. GSK continues to have full responsibility for the development of this

LAG-3OUTLOOK antibody program and Immutep is eligible to receive development-based milestone payments and sales-based royalties. Immutep is advancing strongly towards another step change in 2021. We continue to be in a very strong financial and operational position, following the encouraging clinical results announced for efti in 2020. The discontinuation of the GSK trial has no impact on Immutep’s three other product candidates all of We have increasing confidence in efti and accordingly, over the last six months we have announced or commenced three new efti trials, or trial whichextensions have ,differentwith up to 386 mechanisms patients in different of action,cancer indications. including efti. Immutep’s cash runway is also unimpacted.

Our business development activity has also advanced with a second collaboration with MSD and a new LAG-3 agreement with LabCorp.

16

16 

OUTLOOK

Immutep is advancing strongly towards another step change in 2021. We continue to be in a very strong financial and operational position, following the encouraging clinical results announced for efti in 2020.

We have increasing confidence in efti and accordingly, over the last six months we have announced or commenced three new efti trials, or trial extensions, with up to 386 patients in different cancer indications.

Our business development activity has also advanced with a second collaboration with MSD and a new LAG-3 agreement with LabCorp.

Engagement with regulatory bodies remains a key priority, along with strengthening our IP position and upscaling the manufacturing of efti to prepare for the future. This has already resulted in efti receiving Fast Track designation in 1st line HNSCC from the US FDA, given its encouraging data and potential to meet an unmet medical need.

17 COMPANY CALENDER What’s next

JUNE 4TH 2021 - JUNE 8TH 2021 ASCO 2021 Annual Meeting Immutep will participate in this year`s virtual ASCO 2021 Annual Meeting. https://meetings.asco.org/am/virtual-welcome

JUNE 10TH 2021 - JUNE 18TH 2021 BIO International Convention - Bio Digital 2021 Immutep will participate in the new virtual event format. https://www.bio.org/events/bio-digital

JULY 13TH 2021 - JULY 15TH 2021 Non-Small Cell Lung Cancer (NSCLC) Drug Development Summit Immutep will participate in the digital Non-Small Cell Lung Cancer (NSCLC) Drug Development Summit. Frédéric Triebel, CSO & CMO of Immutep speaks on the subject: A Soluble LAG-3 Protein () with an Anti-PD-1 Antibody (Pembrolizumab): Results of a Phase II Study in NSCLC https://nsclc-drug-development.com/

SEPTEMBER 17TH 2021 - SEPTEMBER 21ST 2021 ESMO 2021 Congress Immutep will participate in the virtual ESMO 2021 congress. https://www.esmo.org/meetings/esmo-congress-2021

NOVEMBER 10TH 2021 - NOVEMBER 14TH 2021 SITC - 36th Annual Meeting & Pre-Conference Programs (SITC 2021) The company will have presentations at the conference and representatives will be attending. Venue: Walter E. Washington Convention Center in Washington, D.C.

18 IMMUTEP Fast Facts

Listings Market Capitalisation Australian Securities Exchange (ASX), NASDAQ A$299.2 million (US$227.5 million) (as of 12 April 2021) Stock Codes ASX: IMM, NASDAQ: IMMP Cash & Term Deposits ~A$54.9 million (~US$42.3 million) (as of 31 Issued Capital – Ordinary Shares December 2020) 672.4 million (as of 12 April 2021)

Board of Directors Senior Management

Russell J Howard, PhD Prof Dr Frédéric Triebel Non-executive Chairman Chief Medical Officer and Chief Scientific Officer

Mr Marc Voigt Deanne Miller Executive Director and Chief Executive Officer Chief Operating Officer, General Counsel and Company Secretary Mr Pete A Meyers Non-executive Director

Grant Chamberlain Non-executive Director

www.immutep.com

19 FOLLOW IMMUTEP’S PROGRESS Immutep is dedicated to maintaining consistent and clear communica- tions with our investors. In addition to our newsletter, we encourage our shareholders to continue following Immutep’s pro- gress in a number of ways: www.immutep.com Our website is a treasure trove for those in search of details about our company, our management team, and archived infor- mation. We encourage everyone to check it out regularly.

www.clinicaltrials.gov Immutep registers all of our clinical trials, and the details of enrolling doctors, on the ClinicalTrials.gov website, a service of the United States National Institutes of Health. This register is the largest such repository of clinical trial information around the world.

Our ClinicalTrials.gov ID for our trials are as follows: • TACTI-mel trial is NCT02676869 • AIPAC trial is NCT02614833 • TACTI-002 trial is NCT03625323 T ACTI-003 trial is NCT04811027

Twitter https://twitter.com/Immutep

Facebook https://www.facebook.com/Immutep/

LinkedIn https://www.linkedin.com/company/857541/