A big year ahead for efti

Immutep 22 November 2018 ADR Update
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Immutep

A big year ahead for efti

Clinical update

Pharma & biotech

 

22 November 2018

ADR research

 

Price

US$2.62

Market cap

US$81m

ADR/Ord conversion ratio 100/1

Gross cash ($m) at 30 September 2018

16.2

ADRs in issue

30.8m

ADR code

IMMP

ADR exchange

NASDAQ

Underlying exchange

ASX

Depository

BNY

ADR share price performance

52-week high/low

$3.90

$1.32

Business description

Immutep is an ASX-listed biotechnology company focused on cancer immunotherapy. Its pipeline is based on four products using an LAG-3 immune control system: IMP321 for cancer chemo-immunotherapy, partnered products IMP731 (GSK) and IMP701 (Novartis), and IMP761 (preclinical).

Next events

TACTI-002 Phase II first patient in

Q119

Initiate INSIGHT-004

Q119

Fully recruit AIPAC breast cancer Phase II

H119

Analysts

Dr Dennis Hulme

+61 (0)2 8249 8345

Maxim Jacobs

+1 646 653 7027

Immutep is a research client of Edison Investment Research Limited

We expect Immutep to deliver on a number of important milestones in the year ahead. The AIPAC Phase II study of its APC activator eftilagimod alpha (efti) plus chemo in breast cancer is expected to complete recruitment in H119 and report top-line data before the end of the year. The TACTI-002 study of efti plus Keytruda in lung and head and neck cancers in collaboration with US Merck will start shortly and report first data mid-year, whereas TACTI-mel will report first data from melanoma patients dosed with efti from the start of Keytruda therapy. Other in-house and partnered programs are also likely to produce significant news. We maintain our valuation of $387m ahead of these milestones.

Year end

Revenue (US$m)

PTP (US$m)

EPADR ($)

DPADR ($)

P/E (x)

Gross yield (%)

06/17

3.1

(6.4)

(0.28)

0.0

N/A

N/A

06/18

5.2

(8.3)

(0.40)

0.0

N/A

N/A

06/19e

8.3

(5.2)

(0.17)

0.0

N/A

N/A

06/20e

2.1

(11.3)

(0.37)

0.0

N/A

N/A

Note: Converted at A$1/US$0.76 for the table above and throughout the note.

AIPAC to report top-line data in 2019

The 226-patient AIPAC study of efti plus paclitaxel in first-line metastatic breast cancer is now over 70% recruited and is expected to fully recruit in H119. Top-line data from the event-driven progression free survival (PFS) analysis is expected to mature in 2019. This will be the first efficacy read-out for efti from a randomized study, so it will be a significant event for the company. The trial could potentially support filing in Europe if it achieves certain (undisclosed) clinical endpoints.

TACTI-002 ready to go

The TACTI-002 Phase II study in collaboration with Merck and Company is on track to recruit the first subjects in early 2019. It will evaluate efti plus Merck’s Keytruda in up to 110 patients with non-small cell lung cancer (NSCLC) or squamous cell carcinoma of the head and neck (SCCHN) at 12–15 sites in the UK, Spain, the US and Australia. Initial data are expected from mid-2019 onwards.

Efti/avelumab combo nears starting line

The INSIGHT-004 study of avelumab plus subcutaneous (SC) efti in 12 patients with a range of advanced solid tumors is expected to start in Q119. The study, in collaboration with Merck KGaA and Pfizer, will be added as the fourth arm of the INSIGHT study (NCT03252938), which is underway at a single site in Germany.

Valuation: Unchanged at $387m, $12.57 per ADR

Our valuation is unchanged at $387m. Our valuation is equal to $12.57 per ADR on an undiluted basis or $9.05 per ADR after diluting for options, warrants and convertible notes. We note that our valuation includes a modest allowance for new indications for efti beyond the ongoing studies in melanoma, lung and head and neck cancers. Gross cash at the end of September 2018 was $16.2m. Our forecasts assume that Immutep receives a risk-adjusted $6m IMP731 milestone payment from GSK in FY19, which would extend its cash reach to the end of FY20.

Durable TACTI-mel responses confirmed

Professor Adnan Khattak, consultant medical oncologist at Fiona Stanley Hospital and a principal investigator of the ongoing Phase I TACTI-mel study, provided an update on the trial in oral and poster presentations at the 33rd Annual Meeting of the Society for Immunotherapy of Cancer (SITC) in Washington, DC, earlier this month.

The response rate was consistent with previous reports, namely a 33% (6/18) overall response rate (ORR) from the start of efti/Keytruda combination therapy, and 61% (11/18) when measured from the start of the 12-week Keytruda monotherapy screening period. These are very encouraging results in a patient population in which 78% (14/18) subjects had M1c (late-stage) metastatic melanoma.

Importantly, the updated data in Exhibit 1 confirm that the tumor responses following efti/Keytruda combination therapy were long lasting. To highlight the new data, we have added green circles to the response plots for selected patients in Exhibit 1 to show the last data point included in the previous data set reported in the investor update in May. None of the patients who achieved a tumor response (50% shrinkage) has experienced significant tumor growth during the period of follow up.

It is interesting to note that one patient with stable disease has seen their tumor start to shrink, 12 months after starting therapy (indicated by a green arrow in Exhibit 1). There is the potential for this patient to develop into a late responder if tumor shrinkage continues.

Part A of the study tested three doses of efti (1, 6 and 30mg/kg) in combination with the anti-PD-1 immune checkpoint inhibitor Keytruda (pembrolizumab, Merck) in 18 patients with advanced melanoma who have had a suboptimal response to initial treatment with Keytruda. In Part A, efti/ Keytruda combination therapy was preceded by 12 weeks of Keytruda monotherapy.

Exhibit 1: Spider plots of tumor responses from cohorts 1–3 of TACTI-mel Part A

Source: SITC poster. Note: pembro = pembrolizumab (Keytruda). We have added green ovals to indicate the last data point for selected patients as shown at the Advances in Immuno-oncology Congress in May. The green arrow indicates the patient with stable disease who is experiencing tumor shrinkage.

Immutep has fully recruited the six-patient cohort that forms Part B of the study. These patients are treated with 30mg efti every two weeks starting at the same time as Keytruda therapy. No dose-limiting toxicities have been observed, which has given Immutep and collaborator Merck and Company confidence that this dose combination is safe to use in the upcoming TACTI-002 study.

No efficacy data from Part B have been reported to date. We expect final TACT-mel data, including Part B efficacy, to be reported in H119.

TACTI-002 to start early 2019; design details presented

The company is finalizing its preparations for its TACTI-002 Phase II study in collaboration with Merck, which is on track to recruit the first subjects in early 2019.

TACTI-002 will evaluate efti plus Keytruda in up to 110 patients with NSCLC or SCCHN at 12–15 sites in the UK, Spain, the US and Australia. Treatment with efti (30mg by subcutaneous injection) will start on the same day as Keytruda treatment in this study, just like in TACTI-mel Part B.

The company presented details of the TACTI-002 trial design in a poster at SITC (Exhibit 2). Patients will receive 18 three-week cycles of efti/Keytruda combination therapy. For the first nine treatment cycles (27 weeks), patient will be injected with efti every two weeks. For the next nine cycles, efti will be administered every three weeks, to align with the Keytruda treatment regimen. At the completion of 54 weeks of combination therapy, patients can receive a further 12 months of Keytruda monotherapy.

Exhibit 2: TACTI-002 trial design

Source: SITC poster. Note: One cycle = three weeks; q2w = every two weeks; q3w = every three weeks

The open-label TACT-002 study will utilize Simon’s two-stage design. For each of the three treatment indications, an initial cohort of 17–23 patients will be treated. For each indication, if the number of patients with tumor responses exceeds the threshold shown in Exhibit 3, additional patients will be recruited to take the total up to ~37 for that indication.

Part A will recruit first-line advanced/metastatic NSCLC patients, who are PD-1/L-1 naive and have not undergone systemic therapy for advanced/metastatic disease.

Part B will recruit second-line advanced/metastatic NSCLC patients who have experienced treatment failure (disease progression) following treatment with any PD-1/PD-L1 regimen.

Part C will recruit second-line SCCHN patients who are PD-1/L1 naive.

The primary endpoint will be ORR (as per irRECIST). The TACTI-002 study will make an important contribution towards building the evidence base to assess whether efti combo therapy can improve response rates to PD-1/L-1 therapy. First data are expected from mid-2019 onwards.

Exhibit 3: Patient numbers and response thresholds for TACTI-002

Indication

Threshold number of responses

Initial number of patients

Threshold response rate

Additional patients

Total patients

Part A: NSCLC first line

4

17

24%

19

36

Part B: NSCLC second line

1

23

4%

13

36

Part C: HNSCC

2

18

11%

19

37

Source: Immutep. Note: HNSCC = head and neck squamous cell carcinoma.

AIPAC data expected H219

The AIPAC Phase IIb breast cancer study is over 70% recruited, with enrolment reaching 160 out of the target of 226 as of the AGM on 16 November. Recruitment passed the halfway mark (113/226) in June and reached 126 (56%) in early August. The company expects recruitment to continue into H119, and the event-driven PFS readout to report in H219 (after 152 PFS events).

The trial is testing the efti soluble LAG-3 fusion protein combined with paclitaxel in women with hormone receptor positive metastatic breast cancer who have not previously received chemotherapy for metastatic disease. The European Medicines Agency has indicated that this trial could be sufficient to support a marketing authorization if it achieves certain (undisclosed) clinical endpoints. A confirmatory Phase III study would likely be required before filing for approval in the US.

LAG525 retained in cutting edge Novartis pipeline

On 30 October Novartis disclosed it was culling 20% of programs from its pipeline to focus its resources on only the most cutting-edge drug candidates. This reduced its drug programs from 430 to 340. Although Novartis has not disclosed a list of the culled programs to the best of our knowledge, all indications are that development of LAG525, which it in-licensed from Immutep, is ongoing.

For example, while the presentation at the Novartis R&D day held the following week (on 5 November) did not specifically mention LAG525, development of its anti-PD-1 drug PDR0011 in multiple combinations in metastatic melanoma was listed among programs with anticipated filings in 2022 or later. In its Q318 results presentation on 18 October, this description referred to trial NCT03484923 in which PDR001 is being trialed in combination with LAG525 or either of two other drugs (Tafinlar or Mekinist) in advanced melanoma patients.

  PDR001 is also known as spartalizumab

Although the R&D day presentation did not specifically mention the other PDR/LAG525 combination studies in other advanced cancers, including breast cancer, according to both the Novartis website and the clinicaltrials.gov database, four trials of LAG525 in combination with PDR001 are recruiting patients, as shown in Exhibit 4. Three of the four studies started recruiting patients in 2018.

LAG525 combo studies are ongoing, which indicates that Novartis considers it has the potential to change the standard of care in high burden disease areas. LAG525 inhibits LAG-3 signaling by blocking the binding of LAG-3 to the MHC class II molecule. Blockade of LAG-3 restores activity of effector T cells, reduces suppressor activity of regulatory T cells and enhances the anti-tumor activity of PD-1 inhibition.

Exhibit 4: Four Novartis PDR001/LAG525 combo studies are currently recruiting subjects

Description

clinicaltrials.gov identifier

Phase

Subjects

Start date

Primary completion

Status

LAG525 +/- PDR001 in advanced solid tumors

NCT02460224

I/II

515

June 2015

July 2019

Recruiting

LAG525 + PDR001 in advanced solid and hematologic cancers

NCT03365791

II

160

January 2018

January 2020

Recruiting

PDR001 + LAG525 or Tafinlar or Mekinist in melanoma

NCT03484923

II

135

September 2018

January 2021

Recruiting

LAG525 +/- PDR001 +/- Carboplatin in TNBC

NCT03499899

II

96

July 2018

December 2019

Recruiting

Source: clinicaltrials.gov. Note: TNBC = triple negative breast cancer

Competing anti-LAG-3 antibodies show further potential

Additional evidence supporting the potential efficacy of anti-PD-1/anti-LAG-3 combo therapy was presented by Novartis’s competitor Merck at SITC.

Merck reported results from a study of its MK-4280 anti-LAG-3 antibody +/- Keytruda in metastatic solid tumors where there was not a clinically effective alternative treatment (clinicaltrials.gov identifier NCT02720068). MK-4280 showed modest activity as a monotherapy (6% ORR, 1/18). The combination of MK-4280 with Keytruda showed promising efficacy, achieving a 27% ORR (4/15) in a range of solid tumors.

Last year BMS reported encouraging results from a Phase I study of its anti-LAG-3 antibody relatlimab (BMS-986016) in melanoma patients who had not responded to or had become resistant to checkpoint inhibitor therapies. In that study, 18% of LAG-3 positive patients responded to combination therapy with relatlimab plus Opdivo, vs a 5% response rate in patients with low tumor LAG-3 expression.2 BMS is undertaking a Phase III study of relatlimab plus Opdivo vs Opdivo alone in 700 patients with untreated advanced melanoma. Top-line results are expected in July 2020.

As we previously noted, Novartis itself reported3 encouraging signs of efficacy from the LAG525 in combination with PDR001 from the Phase I component of its ongoing Phase I/II study (NCT02460224) at ASCO in June. Among the 121 patients with solid tumors treated with LAG525 plus PDR001 at a wide range of doses there were 13 durable responses, including 3/84 mesothelioma patients and 2/5 triple-negative breast cancer patients.

  3/8 includes an additional partial response after the data cut-off date for the conference abstract

We expect Novartis to continue to aggressively pursue its LAG525 clinical trial program as it seeks to ensure it does not allow BMS or Merck to gain a dominant position in the anti-LAG-3 antibody space.

It is important to note that although MK-4280, relatlimab and LAG525 all have a similar mechanism of action (blockade of the LAG-3 immune checkpoint), and are potential competitors to each other, they are not potential competitors to efti, which has a very different mechanism of action.

INSIGHT and the Merck KGaA/Pfizer extension

In September Immutep entered into a clinical trial collaboration and supply agreement with Merck KGaA/Pfizer to investigate the combination of its APC activator efti with their anti-PD-L1 immune checkpoint inhibitor avelumab (Bavencio) in patients with advanced solid tumors. Although avelumab gained FDA approval in 2017 for use in bladder cancer and in the aggressive skin cancer Merkel cell carcinoma, it has not yet been approved in any other cancers.

The study of avelumab plus subcutaneous (SC) efti in 12 patients with a range of advanced solid tumors will be included as an arm of the investigator-sponsored INSIGHT study (NCT03252938), which is underway at a single site in Germany. The combination would fit neatly into INSIGHT, which already includes arms investigating intra-tumoral and intraperitoneal administration of efti, as well as a third arm investigating SC efti in combination with chemo in solid tumors. The avelumab combination therapy arm (INSIGHT-004) is expected to start in Q119 and to report first data in mid-2019.

The principal investigator of the INSIGHT study, including the INSIGHT-004 arm, Professor Dr Salah-Eddin Al-Batran, is a member of Immutep’s clinical advisory board. The main INSIGHT study has already recruited 10 of the target of 38 patients; a status update is expected in coming months.

IMP761 LAG-3 agonist in preclinical development

Immutep has started cell line development and the associated manufacturing steps for IMP761. IMP761 is the first known therapeutic antibody with agonist properties that enable it to activate the LAG-3 receptor on the surface of activated T cells, and thereby downregulate T cell activation and proliferation. In contrast, LAG525 and the other known anti-cancer LAG-3 antibodies are antagonist antibodies that block LAG-3 signaling and thereby prevent the downregulation of T cell immune responses.

The mechanism of action of IMP731 is also different to the company’s partnered IMP731/GSK2831781 cytotoxic antibody, which aims to treat autoimmune disease by killing LAG-3 positive T cells. IMP761 offers the opportunity to fine-tune immune responses, which could benefit sufferers of autoimmune diseases by temporarily switching off activated LAG-3 positive T cells that are damaging tissue or causing inflammation.

Immutep reported in September that preclinical studies of IMP761 in cynomolgus monkeys produced encouraging results that demonstrate the immunosuppressive activity of IMP761 in vivo. Immutep intends to present the preclinical results at a future scientific conference.

Valuation

We maintain our valuation of Immutep at $387m, which is equivalent to $12.57 per ADR on an undiluted basis. On a fully diluted basis our valuation is $9.05 per ADR, after taking into account the options, warrants and convertible notes on issue. Exhibit 5 summarizes the constituent parts of our valuation, which is based on a discount rate of 12.5%. Our valuation assumptions and financial forecasts are unchanged.

Exhibit 5: DCF valuation of Immutep

Value driver

Launch date

Likelihood of success

Peak sales ($m)

Royalty

Value ($m)

Value per ADR

($)

efti-mBC*

2021 (EU), 2024 (US)

35%

971

17.5%

163.6

5.31

efti+anti-PD1 ICI melanoma

2025

15%

480

17.5%

25.3

0.82

efti+Keytruda NSCLC

2025

15%

2,300

17.5%

153.5

4.98

efti+Keytruda ovarian

2027

15%

500

17.5%

18.2

0.59

efti+Keytruda head and neck

2025

15%

470

17.5%

24.8

0.80

efti milestones - assume partnered post PII in MBC

$225m estimated risk-adjusted milestones from out-licensing North American and European rights.

42.3

1.37

IMP731-autoimmune disease

2023

20%

1,079

8%

49.3

1.60

Potential IMP731 milestones from GSK

$90m of total $100m in risk-adjusted milestones from GSK

18.2

0.59

IMP701-solid tumors (lung cancer)

2025

20%

2,440

5%

51.0

1.66

Potential IMP701 milestones from Novartis

$20m in risk-adjusted milestones from Novartis

2.6

0.08

Grants

2.2

0.07

R&D expenses

(16.8)

(0.54)

Admin expenses

(13.0)

(0.42)

Capex

(0.0)

(0.00)

Tax

(141.1)

(4.58)

Net cash

End FY18 net cash (including $10.5m convertible note at face value)

7.4

0.24

Total

387.3

12.57

Source: Edison Investment Research. *mBC = metastatic breast cancer

Exhibit 6 shows that in addition to the 3,081m Immutep shares in issue, there are a further 1,498m potential shares that could be issued on the exercise of options, warrants, performance rights and convertible notes, all of which would be in the money at our $12.57 per ADR undiluted valuation. Exhibit 6 shows that after taking into account these potential shares, our diluted valuation is $9.05 per ADR. Depending on trial progress and the timing of milestone payments from partners, Immutep may require additional funding to complete the efti clinical trials; our diluted valuation of $9.05 per ADR does not take into account potential dilution from any future capital raising.

Exhibit 6: Potential further dilution and value per share

Average exercise price per ADR equivalent ($)

m

Current number of shares

30.8

Ridgeback convertible note potential shares

1.52

6.9

Ridgeback warrants

1.80

3.8

Unlisted warrants

2.51

1.6

Unlisted options

3.81

1.5

Performance rights*

0.00

1.3

Total in-the-money potential shares

15.0

Total potential diluted number of shares

45.8

Net cash raised from options and CN exercise

$27

Valuation (above plus additional cash)

$414

Diluted value per share

$9.05

Source: Edison Investment Research. Note: *Both vested and unvested performance rights have been included.

We include risk-adjusted milestones payable by current partners GSK for IMP731 and Novartis for IMP701, plus milestones from prospective deals for efti. The breadth of the LAG-3 pipeline means there could be further upside if Immutep or its partners launch additional products into the clinic or broaden the indications being studied.

Exhibit 7: Financial summary

 

US$000s

2017

2018

2019e

2020e

Year end 30 June

IFRS

IFRS

IFRS

IFRS

PROFIT & LOSS

Revenue

 

 

3,129

5,209

8,283

2,111

Cost of Sales

(5,720)

(7,592)

(8,352)

(7,935)

Gross Profit

(3,304)

(5,504)

(5,669)

(5,839)

EBITDA

 

 

(5,895)

(8,691)

(5,739)

(11,662)

Operating Profit (before GW and except.)

 

(5,905)

(8,699)

(5,741)

Intangible Amortization

(1,283)

(1,367)

(1,254)

(1,141)

Exceptionals

0

0

0

0

Operating Profit

(7,188)

(10,065)

(6,995)

(12,807)

Other

(571)

245

0

0

Net Interest

79

135

535

379

Profit Before Tax (norm)

 

 

(6,397)

(8,319)

(5,206)

(11,287)

Profit Before Tax (IFRS)

 

 

(7,680)

(9,686)

(6,460)

(12,428)

Tax

560

(1)

0

0

Profit After Tax (norm)

(5,837)

(8,320)

(5,206)

(11,287)

Profit After Tax (IFRS)

(7,119)

(9,687)

(6,460)

(12,428)

0.0

0.0

0.0

0.0

Average Number of Shares Outstanding (m)

2,072.5

2,079.7

3,026.1

Average Number of ADRs Outstanding (m)

20.7

20.8

30.3

EPS - normalized (c)

 

 

(0.3)

(0.4)

(0.2)

(0.4)

EPS - IFRS (c)

 

 

(0.3)

(0.5)

(0.2)

(0.4)

Dividend per share (c)

0.0

0.0

0.0

0.0

Earnings per ADR - normalized ($)

(28.2)

(40.0)

(17.2)

(36.6)

Earnings per ADR - IFRS (c)

(34.4)

(46.6)

(21.3)

(40.3)

Dividend per ADR (c)

0.0

0.0

0.0

0.0

Gross Margin (%)

N/A

N/A

N/A

N/A

EBITDA Margin (%)

N/A

N/A

N/A

N/A

Operating Margin (before GW and except.) (%)

N/A

N/A

N/A

BALANCE SHEET

Fixed Assets

 

 

14,474

13,950

12,704

11,569

Intangible Assets

14,455

13,930

12,676

11,536

Tangible Assets

18

20

27

34

Other

0

0

0

0

Current Assets

 

 

12,099

21,769

16,556

5,262

Stocks

0

0

0

0

Debtors

1,667

2,608

2,608

2,608

Cash

9,300

17,841

12,628

1,335

Other

1,131

1,319

1,319

1,319

Current Liabilities

 

 

(2,001)

(2,929)

(2,929)

(2,929)

Creditors

(1,967)

(2,785)

(2,785)

(2,785)

Short term borrowings

(0)

0

0

0

Short term leases

0

0

0

0

Other

(33)

(144)

(144)

(144)

Long Term Liabilities

 

 

(4,408)

(7,314)

(7,314)

(7,314)

Long term borrowings incl. conv. note

(4,392)

(5,051)

(5,051)

Long term leases

0

0

0

0

Other long term liabilities

(16)

(2,263)

(2,263)

(2,263)

Net Assets

 

 

20,164

25,477

19,017

6,589

CASH FLOW

Operating Cash Flow

 

 

(6,544)

(6,045)

(5,739)

(11,662)

Net Interest

79

135

535

379

Tax

0

0

0

0

Capex

(5)

(9)

(9)

(10)

Acquisitions/disposals

0

0

0

0

Financing

(6)

14,363

0

0

Dividends

0

0

0

0

Other

0

(375)

0

0

Net Cash Flow

(6,477)

8,068

(5,213)

(11,294)

Opening net debt/(cash)

 

 

(12,047)

(4,908)

(12,791)

(7,578)

HP finance leases initiated

0

0

0

0

Other

(663)

(185)

0

0

Closing net debt/(cash)

 

 

(4,908)

(12,791)

(7,578)

3,716

Source: Immutep accounts, Edison Investment Research. Note: Solely for the convenience of the reader the financial summary table has been converted to US$ at a rate of US$0.76 to A$1. Immutep reports statutory accounts in Australian dollars. These translations should not be considered representations that any such amounts have been or could be converted into US dollars at the assumed conversion rate.

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New Zealand

The research in this document is intended for New Zealand resident professional financial advisers or brokers (for use in their roles as financial advisers or brokers) and habitual investors who are “wholesale clients” for the purpose of the Financial Advisers Act 2008 (FAA) (as described in sections 5(c) (1)(a), (b) and (c) of the FAA). This is not a solicitation or inducement to buy, sell, subscribe, or underwrite any securities mentioned or in the topic of this document. For the purpose of the FAA, the content of this report is of a general nature, is intended as a source of general information only and is not intended to constitute a recommendation or opinion in relation to acquiring or disposing (including refraining from acquiring or disposing) of securities. The distribution of this document is not a “personalised service” and, to the extent that it contains any financial advice, is intended only as a “class service” provided by Edison within the meaning of the FAA (i.e. without taking into account the particular financial situation or goals of any person). As such, it should not be relied upon in making an investment decision.

United Kingdom

Neither this document and associated email (together, the "Communication") constitutes or form part of any offer for sale or subscription of, or solicitation of any offer to buy or subscribe for, any securities, nor shall it or any part of it form the basis of, or be relied on in connection with, any contract or commitment whatsoever. Any decision to purchase shares in the Company in the proposed placing should be made solely on the basis of the information to be contained in the admission document to be published in connection therewith.

This Communication is being distributed in the United Kingdom and is directed only at (i) persons having professional experience in matters relating to investments, i.e. investment professionals within the meaning of Article 19(5) of the Financial Services and Markets Act 2000 (Financial Promotion) Order 2005, as amended (the "FPO") (ii) high net-worth companies, unincorporated associations or other bodies within the meaning of Article 49 of the FPO and (iii) persons to whom it is otherwise lawful to distribute it. The investment or investment activity to which this document relates is available only to such persons. It is not intended that this document be distributed or passed on, directly or indirectly, to any other class of persons and in any event and under no circumstances should persons of any other description rely on or act upon the contents of this document (nor will such persons be able to purchase shares in the placing).

This Communication is being supplied to you solely for your information and may not be reproduced by, further distributed to or published in whole or in part by, any other person.

United States

Neither this Communication nor any copy (physical or electronic) of it may be (i) taken or transmitted into the United States of America, (ii) distributed, directly or indirectly, in the United States of America or to any US person (within the meaning of regulations Regulation S made under the US Securities Act 1933, as amended), (iii) taken or transmitted into or distributed in Canada, Australia, the Republic of Ireland or the Republic of South Africa or to any resident thereof, except in compliance with applicable securities laws, (iv) taken or transmitted into or distributed in Japan or to any resident thereof for the purpose of solicitation or subscription or offer for sale of any securities or in the context where the distribution thereof may be construed as such solicitation or offer, or (v) or taken or transmitted into any EEA state other than the United Kingdom. Any failure to comply with these restrictions may constitute a violation of the securities laws or the laws of any such jurisdiction. The distribution of this Communication in or into other jurisdictions may be restricted by law and the persons into whose possession this document comes should inform themselves about, and observe, any such restrictions.

Frankfurt +49 (0)69 78 8076 960

Schumannstrasse 34b

60325 Frankfurt

Germany

London +44 (0)20 3077 5700

280 High Holborn

London, WC1V 7EE

United Kingdom

New York +1 646 653 7026

245 Park Avenue, 39th Floor

10167, New York

US

Sydney +61 (0)2 8249 8342

Level 4

95 Pitt Street, Sydney

NSW 2000, Australia

Frankfurt +49 (0)69 78 8076 960

Schumannstrasse 34b

60325 Frankfurt

Germany

London +44 (0)20 3077 5700

280 High Holborn

London, WC1V 7EE

United Kingdom

New York +1 646 653 7026

245 Park Avenue, 39th Floor

10167, New York

US

Sydney +61 (0)2 8249 8342

Level 4

95 Pitt Street, Sydney

NSW 2000, Australia

General disclaimer and copyright

This report has been commissioned by Immutep and prepared and issued by Edison, in consideration of a fee payable by Immutep. Edison Investment Research standard fees are £49,500 pa for the production and broad dissemination of a detailed note (Outlook) following by regular (typically quarterly) update notes. Fees are paid upfront in cash without recourse. Edison may seek additional fees for the provision of roadshows and related IR services for the client but does not get remunerated for any investment banking services. We never take payment in stock, options or warrants for any of our services.

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No personalised advice: The information that we provide should not be construed in any manner whatsoever as, personalised advice. Also, the information provided by us should not be construed by any subscriber or prospective subscriber as Edison’s solicitation to effect, or attempt to effect, any transaction in a security. The securities described in the report may not be eligible for sale in all jurisdictions or to certain categories of investors.

Investment in securities mentioned: Edison has a restrictive policy relating to personal dealing and conflicts of interest. Edison Group does not conduct any investment business and, accordingly, does not itself hold any positions in the securities mentioned in this report. However, the respective directors, officers, employees and contractors of Edison may have a position in any or related securities mentioned in this report, subject to Edison's policies on personal dealing and conflicts of interest.

Copyright: Copyright 2018 Edison Investment Research Limited (Edison). All rights reserved FTSE International Limited (“FTSE”) © FTSE 2018. “FTSE®” is a trade mark of the London Stock Exchange Group companies and is used by FTSE International Limited under license. All rights in the FTSE indices and/or FTSE ratings vest in FTSE and/or its licensors. Neither FTSE nor its licensors accept any liability for any errors or omissions in the FTSE indices and/or FTSE ratings or underlying data. No further distribution of FTSE Data is permitted without FTSE’s express written consent.

Australia

Edison Investment Research Pty Ltd (Edison AU) is the Australian subsidiary of Edison. Edison AU is a Corporate Authorised Representative (1252501) of Myonlineadvisers Pty Ltd who holds an Australian Financial Services Licence (Number: 427484). This research is issued in Australia by Edison AU and any access to it, is intended only for "wholesale clients" within the meaning of the Corporations Act 2001 of Australia. Any advice given by Edison AU is general advice only and does not take into account your personal circumstances, needs or objectives. You should, before acting on this advice, consider the appropriateness of the advice, having regard to your objectives, financial situation and needs. If our advice relates to the acquisition, or possible acquisition, of a particular financial product you should read any relevant Product Disclosure Statement or like instrument.

New Zealand

The research in this document is intended for New Zealand resident professional financial advisers or brokers (for use in their roles as financial advisers or brokers) and habitual investors who are “wholesale clients” for the purpose of the Financial Advisers Act 2008 (FAA) (as described in sections 5(c) (1)(a), (b) and (c) of the FAA). This is not a solicitation or inducement to buy, sell, subscribe, or underwrite any securities mentioned or in the topic of this document. For the purpose of the FAA, the content of this report is of a general nature, is intended as a source of general information only and is not intended to constitute a recommendation or opinion in relation to acquiring or disposing (including refraining from acquiring or disposing) of securities. The distribution of this document is not a “personalised service” and, to the extent that it contains any financial advice, is intended only as a “class service” provided by Edison within the meaning of the FAA (i.e. without taking into account the particular financial situation or goals of any person). As such, it should not be relied upon in making an investment decision.

United Kingdom

Neither this document and associated email (together, the "Communication") constitutes or form part of any offer for sale or subscription of, or solicitation of any offer to buy or subscribe for, any securities, nor shall it or any part of it form the basis of, or be relied on in connection with, any contract or commitment whatsoever. Any decision to purchase shares in the Company in the proposed placing should be made solely on the basis of the information to be contained in the admission document to be published in connection therewith.

This Communication is being distributed in the United Kingdom and is directed only at (i) persons having professional experience in matters relating to investments, i.e. investment professionals within the meaning of Article 19(5) of the Financial Services and Markets Act 2000 (Financial Promotion) Order 2005, as amended (the "FPO") (ii) high net-worth companies, unincorporated associations or other bodies within the meaning of Article 49 of the FPO and (iii) persons to whom it is otherwise lawful to distribute it. The investment or investment activity to which this document relates is available only to such persons. It is not intended that this document be distributed or passed on, directly or indirectly, to any other class of persons and in any event and under no circumstances should persons of any other description rely on or act upon the contents of this document (nor will such persons be able to purchase shares in the placing).

This Communication is being supplied to you solely for your information and may not be reproduced by, further distributed to or published in whole or in part by, any other person.

United States

Neither this Communication nor any copy (physical or electronic) of it may be (i) taken or transmitted into the United States of America, (ii) distributed, directly or indirectly, in the United States of America or to any US person (within the meaning of regulations Regulation S made under the US Securities Act 1933, as amended), (iii) taken or transmitted into or distributed in Canada, Australia, the Republic of Ireland or the Republic of South Africa or to any resident thereof, except in compliance with applicable securities laws, (iv) taken or transmitted into or distributed in Japan or to any resident thereof for the purpose of solicitation or subscription or offer for sale of any securities or in the context where the distribution thereof may be construed as such solicitation or offer, or (v) or taken or transmitted into any EEA state other than the United Kingdom. Any failure to comply with these restrictions may constitute a violation of the securities laws or the laws of any such jurisdiction. The distribution of this Communication in or into other jurisdictions may be restricted by law and the persons into whose possession this document comes should inform themselves about, and observe, any such restrictions.

Frankfurt +49 (0)69 78 8076 960

Schumannstrasse 34b

60325 Frankfurt

Germany

London +44 (0)20 3077 5700

280 High Holborn

London, WC1V 7EE

United Kingdom

New York +1 646 653 7026

245 Park Avenue, 39th Floor

10167, New York

US

Sydney +61 (0)2 8249 8342

Level 4

95 Pitt Street, Sydney

NSW 2000, Australia

Frankfurt +49 (0)69 78 8076 960

Schumannstrasse 34b

60325 Frankfurt

Germany

London +44 (0)20 3077 5700

280 High Holborn

London, WC1V 7EE

United Kingdom

New York +1 646 653 7026

245 Park Avenue, 39th Floor

10167, New York

US

Sydney +61 (0)2 8249 8342

Level 4

95 Pitt Street, Sydney

NSW 2000, Australia

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