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Merck collaboration opens new opportunities

Immutep 29 March 2018 Update
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Immutep

Merck collaboration opens new opportunities

Merck collaboration

Pharma & biotech

29 March 2018

Price

A$0.023

Market cap

A$62m

US$0.76/A$

Gross cash (A$m) at 31 December 2017

13.7

Shares in issue

2,725.5m

Free float

87%

Code

IMM

Primary exchange

ASX

Secondary exchange

NASDAQ

Share price performance

%

1m

3m

12m

Abs

9.1

0.0

(25.0)

Rel (local)

6.7

0.1

(28.6)

52-week high/low

A$84.5

A$35.5

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-mel cohort 3 safety and activity data

Q218

Fully recruit AIPAC breast cancer Phase II

mid-2018

Initiate TACTI-002 Phase II

H218

Analysts

Dr Dennis Hulme

+61 (0)2 9258 1161

Maxim Jacobs

+1 646 653 7027

Immutep is a research client of Edison Investment Research Limited

Immutep has entered a clinical trial collaboration and supply agreement with Merck & Co (MSD) for a Phase II study to evaluate eftilagimod alpha (IMP321) plus Keytruda in lung, head and neck and ovarian cancers. It is positive to see Immutep collaborating with a leading immunotherapy company, with three new indications added to its ongoing studies in breast cancer and melanoma. It has raised A$6.9m through a placement and has opened a share purchase plan to raise up to A$10m. We increase our valuation to A$439m (vs A$272m) or A$0.14/share (vs A$0.12/share).

Year
end

Revenue
(A$m)

PBT*
(A$m)

EPS*
(c)

DPS*
(c)

P/E
(x)

Yield
(%)

06/16

1.9

(13.7)

(0.6)

0.0

N/A

N/A

06/17

4.1

(8.4)

(0.4)

0.0

N/A

N/A

06/18e

3.5

(12.9)

(0.6)

0.0

N/A

N/A

06/19e

10.9

(6.4)

(0.2)

0.0

N/A

N/A

Note: *PBT and EPS are normalised, excluding exceptionals and share-based payments.

Phase II in collaboration with Merck to begin H218

Immutep and Merck will collaborate in the TACTI-002 Phase II study of IMP321 plus Keytruda in up to 120 patients with non-small cell lung cancer (NSCLC), head and neck cancer or ovarian cancer. In clinical studies IMP321 has been shown to stimulate the immune system and turn “cold” tumours “hot”. There is good potential for response rates in these three cancers to be increased by combining the immune activation activity of IMP321 with an immune checkpoint inhibitor such as Keytruda, particularly in patients with low levels of PDL1 expression in tumours.

TACTI-mel Phase I study expanded, data update in Q2

The three-dose escalation cohorts in the TACTI-mel study of IMP321 plus Keytruda in melanoma are fully recruited and the Database Safety and Monitoring Board has confirmed that the highest dose (30mg) is safe and well tolerated. In 2017 the company reported an encouraging 33% response rate in the first two cohorts of patients who had a suboptimal initial response to Keytruda monotherapy; further data, including initial cohort three results, are expected in Q218. Immutep has recruited the first subject in an additional cohort of six patients to be dosed with IMP321 from the first cycle of Keytruda therapy vs the fifth cycle previously.

SPP to extend funding runway beyond AIPAC readout

The AIPAC breast cancer Phase II is expected to fully recruit in mid-2018 and report top-line progression free survival data by mid-2019. The cash from the institutional placement (A$6.9m before costs) and share purchase plan (SPP) (up to A$10m) aims to extend the funding runway to late CY19, excluding any further milestone payments from partners Novartis and GlaxoSmithKline. Milestone revenue (we model ~A$8m in FY19) would extend the cash runway.

Valuation: Increased to A$439m, 14c per share

We have rolled forward our DCF model, added the three new IMP321 indications and updated our forecasts for the capital raise and H118 results. Our valuation has increased to A$439m (vs A$272m) or A$0.14/share (vs A$0.12/share).

Merck collaboration opens up new indications

On 12 March Immutep announced that it had entered a clinical trial collaboration and supply agreement with MSD for a Phase II study of IMP321 plus Merck’s anti-PD1 immune checkpoint inhibitor (ICI) Keytruda in patients with NSCLC, head and neck cancer or ovarian cancer.

The Phase II study, referred to as TACTI-002, will recruit up to 120 patients in the US and Europe across the three indications in an open label single-arm Simon two-stage design. In the first stage of a Simon two-stage study, a small number of patients with each disease type is treated. If a predefined threshold response rate is observed in this initial cohort, a larger number of patients is recruited in the second stage of the study. If the response rate in the first stage does not reach the predefined threshold for a particular indication, no further patients with that cancer type are recruited.

It seems likely that the indications that were chosen for the TACTI-002 study are the ones where Merck and Immutep see the greatest potential benefit from combining a therapy such as IMP321, which can turn immunologically cold tumours hot, with Keytruda to increase the response rate. It is noteworthy that response rates reported for single-agent ICI therapy in ovarian and head and neck cancers have been quite low (10-16%), while in NSCLC response rates have been low in patients with low levels of PDL1 expression in their tumours.

No details regarding the financial terms of the collaboration have been disclosed. We assume that Merck will provide the Keytruda medication, while Immutep will manage the study and be responsible for most of the other trial costs. We estimate that Immutep’s contribution to the trial is likely to be around US$10m if the full number of 120 patients is recruited.

Lung cancer represents a large potential market

According to the National Cancer Institute, lung cancer is the second most common cancer (after breast cancer), with 222,500 new cases per year in the US. The poor prognosis for lung cancer patients (five-year survival rate 18%) means it is responsible for more deaths than any other cancer, with 156,000 deaths each year in the US. The collaboration with Merck is targeting NSCLC which accounts for ~85% of cases of lung cancer.

A number of ICI therapies have already been approved for treating NSCLC. Keytruda itself already has first-line approvals both as a single agent and in tandem with chemotherapy.

Keytruda monotherapy is approved as a first-line therapy in NSCLC patients who have a high level of PDL1 expression (>50%) in their tumours. In this setting Keytruda achieved an overall response rate (ORR) of 45% vs 28% for chemotherapy control.

In combination with chemotherapy, Keytruda is approved as a first-line treatment for NSCLC patients regardless of PDL1 tumour expression status, having achieved an ORR 55% vs 29% for chemotherapy alone.

Given the large number of lung cancer patients, any treatment that improves response rates in this patient group could be particularly valuable. We note that the good tolerability observed for IMP321 in studies so far could see it used (if effective) as part of triple combos of Keytruda/chemo/IMP321 to further improve response rates. The good tolerability could also see the IMP321/Keytruda combination used as an alternative to Keytruda/chemotherapy.

No ICI therapies approved in ovarian cancer to date

Ovarian cancer accounts for 22,400 new cases and 14,100 deaths in the US each year, with a five-year survival rate of 47%. No ICI drugs have been approved for ovarian cancer. Response rates reported for single-agent ICI therapy from early-stage trials have been modest at ~10-15%1.

  Gaillard et al. Gynecologic Oncology Research and Practice (2016) 3:11

We see the potential for accelerated approval of an IMP321/Keytruda combination in ovarian cancer if the combination substantially improves response rates, given the high unmet need in this disease.

The most advanced ICI trial in ovarian cancer is Phase III JAVELIN Ovarian 200 study of Pfizer’s Bavencio (avelumab), anti-PD-L1 ICI drug alone or in combination with pegylated liposomal doxorubicin chemotherapy (NCT02580058). This 550-patient study has an estimated completion date of March 2018, so top-line data could be available in the next few months.

Low response rates to ICI therapy in head and neck cancer

There are 63,000 new cases of head and neck cancer and 13,300 deaths in the US each year, with a five-year survival rate of ~60%. Keytruda and Bristol-Myers Squibb’s ICI drug Opdivo (nivolumab) were both approved in 2016 for patients with advanced head and neck cancer. However, the response rates to single-agent ICI therapy in this condition are low. Keytruda reported an ORR of 16% and complete response rate of 5% in a single-arm pivotal trial in 174 patients, whereas Opdivo achieved an ORR of 13% vs 6% in a chemotherapy control group.

Viralytics/Merck deal is consistent with our valuation of Immutep

It is relevant to note that in February Merck agreed to acquire the Australian cancer immunotherapy company Viralytics for A$502m (US$394m). The agreed price of A$1.75 per share was a 160% premium to the one month volume weighted average price of Viralytics’ shares. Viralytics is developing the Cavatak oncolytic virus in multiple Phase I and Phase II trials, including in combination with Merck’s Keytruda and BMS’s anti-CTLA4 drug Yervoy (ipilimumab). Ongoing trials are targeting melanoma, NSCLC and bladder cancer, while Phase I studies in colorectal cancer liver metastases and head and neck cancer are planned to commence in 2018.

In an interesting parallel with Immutep, Viralytics entered a clinical trial collaboration agreement with Merck in November 2015 to evaluate the safety and efficacy of Cavatak combined with Keytruda in NSCLC and metastatic bladder cancer patients. In a similar strategy to the IMP321/Keytruda combination, Viralytics was seeking to increase tumour response rates by combining Cavatak immunotherapy with Keytruda.

Our A$439m valuation of Immutep is approximately six times higher than the estimated post-SPP market capitalisation of the company of ~A$74m (at the current market price of 2.3c per share). Given the parallels in the drug development strategies of the two companies, the Merck/Viralytics transaction gives us comfort that our valuation of Immutep is reasonable.

Novartis expands partnered anti-LAG-3 programme to include a Phase II trial

Novartis is developing LAG525, an anti-LAG-3 antibody that is based on a programme that it in-licensed from Immutep. LAG525 blocks the LAG-3-mediated inhibitory signal given to tumour-infiltrating T cells and thus activates T-cell proliferation.

Novartis is conducting a 515-patient Phase I/II trial of LAG525. The trial (clinicaltrials.gov identifier: NCT02460224) is testing LAG525 in combination with Novartis’s in-development anti-PD-1 ICI PDR001. The Phase II component of the study was initially targeting patients with melanoma, NSCLC and renal cancers, but in September 2017 the protocol was expanded to enrol patients with mesothelioma and triple-negative breast cancer. The trial began in June 2015 and has an estimated completion date of April 2019 (previously October 2018).

In January Novartis initiated a 160-patient open label Phase II study of PDR001+LAG525 in multiple tumour types. The trial (clinicaltrials.gov identifier: NCT03365791) is enrolling patients with gastric, lung, prostate, oesophageal and ovarian cancers, as well as neuroendocrine tumours and lymphoma.

To our knowledge, Novartis has not yet published any results from the initial LAG525 combination study, but the recent initiation of the second LAG525 clinical trial is evidence that the LAG525 programme is progressing as anticipated.

IMP731/GSK2831781 Phase I in psoriasis ongoing

GlaxoSmithKline (GSK) is conducting a Phase I trial of GSK2831781, which is based on LAG-3 technology in-licensed from Immutep. GSK2831781 is a cytotoxic monoclonal antibody (mAb) that will kill the few LAG-3+ activated T cells that infiltrate autoimmune disease sites. The estimated completion date for the study is listed as March 2018 on the GSK clinical studies register, so the trial may have recently been completed and there may be some newsflow from this project in the near term.

The trial was designed to measure the activity of escalating doses of GSK2831781 in patients with the autoimmune disease plaque psoriasis, including the proportion of patients achieving 50% and 75% improvement from baseline in Psoriasis Area Severity Index, and change from baseline in Psoriatic Lesion Severity Scores. This suggests that the Phase I trial could potentially produce early evidence of activity of the therapy in psoriasis patients.

Following a portfolio review, GSK announced in July 2017 that around 30 drug development programmes were to be terminated or divested. The LAG-3 programme has been retained, which suggests the company is satisfied with the way the Phase I trial is progressing.

IMP761 LAG-3 agonist in preclinical development

Immutep has developed IMP761, which is a humanised mAb that acts as an agonist to stimulate the activity of the LAG-3 receptor. The mechanism of action is different from other known LAG-3 antibodies; 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 down regulate T cell activation and proliferation. In contrast, LAG525 and the other known therapeutic LAG-3 antibodies are antagonist antibodies which block LAG-3 signalling and thereby prevent the downregulation of T cell immune responses.

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

IMP761 is undergoing preclinical development to better understand its potential applications; new preclinical data are expected to be reported in 2018.

Valuation

Our valuation of Immutep has increased to A$439m (previously A$272m) or 14c per share (undiluted) (vs 12c per share). On a fully diluted basis our valuation is 10c per share (vs 8c per share previously), after taking into account the options, warrants and convertible notes on issue. Exhibit 1 summarises the constituent parts of our valuation, which is based on a discount rate of 12.5%.

We have rolled our risk-adjusted NPV model forward in time and have updated our financial forecast to account for the (~A$6.9m) institutional placement in March. We have also assumed that the current SPP will raise A$10m (before costs) through the issue of 476.2m shares at A$0.021 per share, which would increase the 2,725.5m shares that are currently on issue following the institutional placement to a total of 3,202m.

We forecast the gross cash balance at end FY18 to be A$21.2m. For valuation purposes we deduct the A$13.75m face value of the Ridgeback Capital convertible note in calculating end-FY18 net debt of A$7.5m as shown in Exhibit 1. We note that this is different to the accounting treatment of the convertible note, which includes only the A$6.2m estimated fair value of the convertible note as a non-current liability with the remainder treated as equity, resulting in a balance sheet net cash figure of A$15.5m as shown in Exhibit 3.

We have added NSCLC, ovarian cancer and head and neck cancer indications for IMP321 in combination with Keytruda following the announcement of the planned TACTI-002 Phase II study in these indications. We assume a modest 15% probability of success in these indications, which we may revise upwards as more information becomes available. We base our estimate of market size on the number of deaths from these cancers (rather than the number of new cases). We assume a 20% peak penetration for ovarian and head and neck cancers, and a lower 10% penetration in NSCLC due to the number of competing immunotherapies in the market and assume a pricing of US$60k per patient in the US market. We assume that US market represents 50% of global sales.

Our peak sales estimates for IMP321 in melanoma and for IMP701/LAG525 and IMP731 are unchanged.

Exhibit 1: DCF valuation of Immutep

Value driver

Launch date

Likelihood of success

Peak sales (US$m)

Royalty

Value

(A$m)

Value per share

(A$)

IMP321-MBC*

2021 (EU),
2024 (US)

35%

971

17.5%

204.9

0.06

IMP321+anti-PD1 ICI-melanoma

2025

15%

480

17.5%

31.7

0.01

IMP321+Keytruda NSCLC

2025

15%

2,300

17.5%

153.8

0.05

IMP321+Keytruda ovarian

2025

15%

500

17.5%

32.7

0.01

IMP321+head and neck

2025

15%

470

17.5%

31.0

0.01

IMP321 milestones - assume partnered post PII in MBC

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

53.0

0.02

IMP731-autoimmune disease

2023

15%

1,079

8%

46.3

0.01

Potential IMP731 milestones from GSK

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

19.2

0.01

IMP701-solid tumours (lung cancer)

2025

15%

2,440

5%

47.9

0.01

Potential IMP701 milestones from Novartis

US$20m in risk-adjusted milestones from Novartis

3.2

0.00

Grants

2.7

0.00

R&D expenses

(20.6)

(0.01)

Admin expenses

(15.6)

(0.00)

Capex

(0.0)

(0.00)

Tax

(159.1)

(0.05)

Net cash

End FY18 net cash (including A$13.75m convertible note at face value, assumes SPP raises A$10m)

7.5.0

0.00

Total

438.6

0.14

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

Exhibit 2 shows that in addition to the 3,202m Immutep shares that would be on issue if, as we assume, the SPP raises A$10m. There are a further 1,546m 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 14c per share undiluted valuation. Exhibit 2 shows that after taking into account these potential shares, our diluted valuation is 10c per share. Depending on trial progress and the timing of milestone payments from partners, Immutep may require additional funding to complete the IMP321 clinical trials; our diluted valuation of 10c per share does not take into account potential dilution from any future capital raising.

Exhibit 2: Potential further dilution and value per share

Average exercise price (A$)

m

Current number of shares

3,202

Ridgeback convertible note potential shares

0.020

688

Ridgeback warrants

0.024

380

Listed options

0.200

197

Unlisted options

0.050

151

Performance rights*

0.000

130

Total in-the-money potential shares

1,546

Total potential diluted number of shares

4,748

Net cash raised from options and CN exercise

A$37

Valuation (above plus additional cash)

A$475

Diluted value per share

A$0.10

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

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.

We include risk-adjusted milestones payable by current partners GSK for IMP731 and Novartis for IMP701, plus milestones from prospective deals for IMP321. Possible catalysts include efficacy data from the AIPAC dose-finding cohorts, progression of the licensed anti-LAG-3 antibody into Phase II by GSK or news on partnering, all of which could provide upside to our current valuation.

Financials

Immutep’s gross cash position at the end of December 2017 was A$13.7m. Since then it has received gross cash proceeds of ~A$6.9m from a placement to institutional investors and has initiated an SPP that aims to raise A$10m. Operating cash burn in H1 FY18 was A$4.5m, 8% higher than in the previous year.

We have increased forecast R&D expenditure in line with the increase spend in H1 FY18 and the announcement of the TACTI-002 Phase II study to commence in H2 CY18. We have also increased forecast SG&A spend in line with increased expenditure in H1 FY18. These changes see our forecast FY18 EBITDA loss increase to A$13.2m (vs A$8.7m). We forecast an A$7.1m EBITDA loss in FY19.

Company guidance is that if the SPP raises A$10m then would have a projected cash reach to late CY19. Our forecasts assume that Immutep receives a risk-adjusted US$6m (A$8m) milestone payment from GSK in FY19 under the IMP731/GSK2831781 licence agreement, which would extend its cash reach to the end of FY20.

Sensitivities

Immutep is exposed to the same clinical, regulatory and commercialisation risks as all biotech companies. The key sensitivity is clinical progress of its pipeline of LAG-3 candidates, primarily the internally funded IMP321. While Immutep has funds to conduct the IMP321 Phase II study in metastatic breast cancer, it would require a partnership or alternative forms of funding to advance this indication further. Existing partnerships with big pharma reduce the financial and execution risk for IMP701 and IMP731; in addition, if the Phase I study of IMP701 reveals evidence of efficacy, it could lead GSK to extend the study to additional indications including rheumatoid arthritis and multiple sclerosis, which could increase the potential peak sales and therefore the value of the product.

Exhibit 3: Financial summary

A$'000s

2015

2016

2017

2018e

2019e

Year end 30 June

IFRS

IFRS

IFRS

IFRS

IFRS

PROFIT & LOSS

Revenue

 

 

1,336

1,949

4,117

3,500

10,855

R&D expenses

(8,952)

(7,060)

(7,526)

(9,752)

(10,752)

SG&A expenses

(5,723)

(6,983)

(4,347)

(6,977)

(7,187)

EBITDA

 

 

(13,345)

(12,093)

(7,756)

(13,229)

(7,083)

Operating Profit (before GW and except.)

 

(13,671)

(12,275)

(7,770)

(13,232)

(7,086)

Intangible Amortisation

(1,015)

(1,993)

(1,688)

(1,712)

(1,558)

Exceptionals

(18,338)

(47,468)

0

0

0

Operating Profit

(33,024)

(61,736)

(9,458)

(14,944)

(8,644)

Other

538

(1,716)

(752)

0

0

Net Interest

192

256

104

367

638

Profit Before Tax (norm)

 

 

(12,940)

(13,735)

(8,417)

(12,865)

(6,449)

Profit Before Tax (IFRS)

 

 

(32,294)

(63,196)

(10,105)

(14,577)

(8,006)

Tax

142

1,181

737

0

0

Profit After Tax (norm)

(12,798)

(12,554)

(7,680)

(12,865)

(6,449)

Profit After Tax (IFRS)

(32,152)

(62,015)

(9,368)

(14,577)

(8,006)

Average Number of Shares Outstanding (m)

1,490.1

2,016.6

2,072.5

2,079.7

3,201.7

EPS - normalised (c)

 

 

(0.9)

(0.6)

(0.4)

(0.6)

(0.2)

EPS - IFRS (c)

 

 

(2.2)

(3.1)

(0.5)

(0.7)

(0.3)

Dividend per share (c)

0.0

0.0

0.0

0.0

0.0

Gross Margin (%)

N/A

N/A

N/A

N/A

N/A

EBITDA Margin (%)

N/A

N/A

N/A

N/A

N/A

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

N/A

N/A

N/A

N/A

N/A

BALANCE SHEET

Fixed Assets

 

 

22,960

20,883

19,045

17,337

15,783

Intangible Assets

22,662

20,852

19,020

17,309

15,751

Tangible Assets

298

32

24

28

32

Other

0

0

0

0

0

Current Assets

 

 

8,023

21,671

15,919

24,938

18,485

Stocks

0

0

0

0

0

Debtors

315

168

2,194

2,194

2,194

Cash

6,760

20,880

12,237

21,256

14,803

Other

948

623

1,488

1,488

1,488

Current Liabilities

 

 

(4,380)

(1,472)

(2,632)

(2,632)

(2,632)

Creditors

(2,791)

(1,444)

(2,589)

(2,589)

(2,589)

Short term borrowings

(1,508)

(0)

(0)

(0)

(0)

Short term leases

0

0

0

0

0

Other

(80)

(28)

(43)

(43)

(43)

Long Term Liabilities

 

 

(1,914)

(5,765)

(5,799)

(6,231)

(6,231)

Long term borrowings incl. conv. note

0

(5,027)

(5,779)

(6,211)

(6,211)

Long term leases

0

0

0

0

0

Other long term liabilities

(1,914)

(737)

(20)

(20)

(20)

Net Assets

 

 

24,690

35,317

26,532

33,411

25,404

CASH FLOW

Operating Cash Flow

 

 

(7,785)

(11,594)

(8,611)

(13,229)

(7,083)

Net Interest

0

284

104

367

638

Tax

(2)

0

0

0

0

Capex

(49)

(27)

(7)

(7)

(7)

Acquisitions/disposals

(20,913)

130

0

0

0

Financing

7,745

27,229

(9)

21,888

0

Dividends

0

0

0

0

0

Other

(164)

0

0

0

0

Net Cash Flow

(21,168)

16,022

(8,522)

9,019

(6,453)

Opening net debt/(cash)

 

 

(23,200)

(5,251)

(15,852)

(6,458)

(15,044)

HP finance leases initiated

0

0

0

0

0

Other

3,220

(5,421)

(872)

(432)

0

Closing net debt/(cash)

 

 

(5,251)

(15,852)

(6,458)

(15,044)

(8,592)

Source: Company accounts, Edison Investment Research

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DISCLAIMER
Copyright 2018 Edison Investment Research Limited. All rights reserved. This report has been commissioned by Immutep and prepared and issued by Edison for publication globally. All information used in the publication of this report has been compiled from publicly available sources that are believed to be reliable, however we do not guarantee the accuracy or completeness of this report. Opinions contained in this report represent those of the research department of Edison at the time of publication. The securities described in the Investment Research may not be eligible for sale in all jurisdictions or to certain categories of investors.
This research is issued in Australia by Edison Investment Research Pty Ltd (Corporate Authorised Representative (1252501) of Myonlineadvisers Pty Ltd (AFSL: 427484)) and any access to it, is intended only for "wholesale clients" within the meaning of the Corporations Act 2001 of Australia. The Investment Research is distributed in the United States by Edison US to major US institutional investors only. Edison US is registered as an investment adviser with the Securities and Exchange Commission. Edison US relies upon the "publishers' exclusion" from the definition of investment adviser under Section 202(a)(11) of the Investment Advisers Act of 1940 and corresponding state securities laws. As such, Edison does not offer or provide personalised advice. We publish information about companies in which we believe our readers may be interested and this information reflects our sincere opinions. The information that we provide or that is derived from our website is not intended to be, and should not be construed in any manner whatsoever as, personalised advice. Also, our website and 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 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. This document is provided for information purposes only and should not be construed as an offer or solicitation for investment in any securities mentioned or in the topic of this document. A marketing communication under FCA Rules, this document has not been prepared in accordance with the legal requirements designed to promote the independence of investment research and is not subject to any prohibition on dealing ahead of the dissemination of investment research. Edison has a restrictive policy relating to personal dealing. 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. Edison or its affiliates may perform services or solicit business from any of the companies mentioned in this report. The value of securities mentioned in this report can fall as well as rise and are subject to large and sudden swings. In addition it may be difficult or not possible to buy, sell or obtain accurate information about the value of securities mentioned in this report. Past performance is not necessarily a guide to future performance. Forward-looking information or statements in this report contain information that is based on assumptions, forecasts of future results, estimates of amounts not yet determinable, and therefore involve known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of their subject matter to be materially different from current expectations. 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 (ie 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. To the maximum extent permitted by law, Edison, its affiliates and contractors, and their respective directors, officers and employees will not be liable for any loss or damage arising as a result of reliance being placed on any of the information contained in this report and do not guarantee the returns on investments in the products discussed in this publication. 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.

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

295 Madison Avenue, 18th Floor

10017, New York

US

Sydney +61 (0)2 8249 8342

Level 12, Office 1205

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

295 Madison Avenue, 18th Floor

10017, New York

US

Sydney +61 (0)2 8249 8342

Level 12, Office 1205

95 Pitt Street, Sydney

NSW 2000, Australia

Edison is an investment research and advisory company, with offices in North America, Europe, the Middle East and AsiaPac. The heart of Edison is our world-renowned equity research platform and deep multi-sector expertise. At Edison Investment Research, our research is widely read by international investors, advisers and stakeholders. Edison Advisors leverages our core research platform to provide differentiated services including investor relations and strategic consulting. Edison is authorised and regulated by the Financial Conduct Authority. Edison Investment Research (NZ) Limited (Edison NZ) is the New Zealand subsidiary of Edison. Edison NZ is registered on the New Zealand Financial Service Providers Register (FSP number 247505) and is registered to provide wholesale and/or generic financial adviser services only. Edison Investment Research Inc (Edison US) is the US subsidiary of Edison and is regulated by the Securities and Exchange Commission. Edison Investment Research Limited (Edison Aus) [46085869] is the Australian subsidiary of Edison. Edison Germany is a branch entity of Edison Investment Research Limited [4794244]. www.edisongroup.com

DISCLAIMER
Copyright 2018 Edison Investment Research Limited. All rights reserved. This report has been commissioned by Immutep and prepared and issued by Edison for publication globally. All information used in the publication of this report has been compiled from publicly available sources that are believed to be reliable, however we do not guarantee the accuracy or completeness of this report. Opinions contained in this report represent those of the research department of Edison at the time of publication. The securities described in the Investment Research may not be eligible for sale in all jurisdictions or to certain categories of investors.
This research is issued in Australia by Edison Investment Research Pty Ltd (Corporate Authorised Representative (1252501) of Myonlineadvisers Pty Ltd (AFSL: 427484)) and any access to it, is intended only for "wholesale clients" within the meaning of the Corporations Act 2001 of Australia. The Investment Research is distributed in the United States by Edison US to major US institutional investors only. Edison US is registered as an investment adviser with the Securities and Exchange Commission. Edison US relies upon the "publishers' exclusion" from the definition of investment adviser under Section 202(a)(11) of the Investment Advisers Act of 1940 and corresponding state securities laws. As such, Edison does not offer or provide personalised advice. We publish information about companies in which we believe our readers may be interested and this information reflects our sincere opinions. The information that we provide or that is derived from our website is not intended to be, and should not be construed in any manner whatsoever as, personalised advice. Also, our website and 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 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. This document is provided for information purposes only and should not be construed as an offer or solicitation for investment in any securities mentioned or in the topic of this document. A marketing communication under FCA Rules, this document has not been prepared in accordance with the legal requirements designed to promote the independence of investment research and is not subject to any prohibition on dealing ahead of the dissemination of investment research. Edison has a restrictive policy relating to personal dealing. 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. Edison or its affiliates may perform services or solicit business from any of the companies mentioned in this report. The value of securities mentioned in this report can fall as well as rise and are subject to large and sudden swings. In addition it may be difficult or not possible to buy, sell or obtain accurate information about the value of securities mentioned in this report. Past performance is not necessarily a guide to future performance. Forward-looking information or statements in this report contain information that is based on assumptions, forecasts of future results, estimates of amounts not yet determinable, and therefore involve known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of their subject matter to be materially different from current expectations. 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 (ie 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. To the maximum extent permitted by law, Edison, its affiliates and contractors, and their respective directors, officers and employees will not be liable for any loss or damage arising as a result of reliance being placed on any of the information contained in this report and do not guarantee the returns on investments in the products discussed in this publication. 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.

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

295 Madison Avenue, 18th Floor

10017, New York

US

Sydney +61 (0)2 8249 8342

Level 12, Office 1205

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

295 Madison Avenue, 18th Floor

10017, New York

US

Sydney +61 (0)2 8249 8342

Level 12, Office 1205

95 Pitt Street, Sydney

NSW 2000, Australia

Edison is an investment research and advisory company, with offices in North America, Europe, the Middle East and AsiaPac. The heart of Edison is our world-renowned equity research platform and deep multi-sector expertise. At Edison Investment Research, our research is widely read by international investors, advisers and stakeholders. Edison Advisors leverages our core research platform to provide differentiated services including investor relations and strategic consulting. Edison is authorised and regulated by the Financial Conduct Authority. Edison Investment Research (NZ) Limited (Edison NZ) is the New Zealand subsidiary of Edison. Edison NZ is registered on the New Zealand Financial Service Providers Register (FSP number 247505) and is registered to provide wholesale and/or generic financial adviser services only. Edison Investment Research Inc (Edison US) is the US subsidiary of Edison and is regulated by the Securities and Exchange Commission. Edison Investment Research Limited (Edison Aus) [46085869] is the Australian subsidiary of Edison. Edison Germany is a branch entity of Edison Investment Research Limited [4794244]. www.edisongroup.com

DISCLAIMER
Copyright 2018 Edison Investment Research Limited. All rights reserved. This report has been commissioned by Immutep and prepared and issued by Edison for publication globally. All information used in the publication of this report has been compiled from publicly available sources that are believed to be reliable, however we do not guarantee the accuracy or completeness of this report. Opinions contained in this report represent those of the research department of Edison at the time of publication. The securities described in the Investment Research may not be eligible for sale in all jurisdictions or to certain categories of investors.
This research is issued in Australia by Edison Investment Research Pty Ltd (Corporate Authorised Representative (1252501) of Myonlineadvisers Pty Ltd (AFSL: 427484)) and any access to it, is intended only for "wholesale clients" within the meaning of the Corporations Act 2001 of Australia. The Investment Research is distributed in the United States by Edison US to major US institutional investors only. Edison US is registered as an investment adviser with the Securities and Exchange Commission. Edison US relies upon the "publishers' exclusion" from the definition of investment adviser under Section 202(a)(11) of the Investment Advisers Act of 1940 and corresponding state securities laws. As such, Edison does not offer or provide personalised advice. We publish information about companies in which we believe our readers may be interested and this information reflects our sincere opinions. The information that we provide or that is derived from our website is not intended to be, and should not be construed in any manner whatsoever as, personalised advice. Also, our website and 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 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. This document is provided for information purposes only and should not be construed as an offer or solicitation for investment in any securities mentioned or in the topic of this document. A marketing communication under FCA Rules, this document has not been prepared in accordance with the legal requirements designed to promote the independence of investment research and is not subject to any prohibition on dealing ahead of the dissemination of investment research. Edison has a restrictive policy relating to personal dealing. 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. Edison or its affiliates may perform services or solicit business from any of the companies mentioned in this report. The value of securities mentioned in this report can fall as well as rise and are subject to large and sudden swings. In addition it may be difficult or not possible to buy, sell or obtain accurate information about the value of securities mentioned in this report. Past performance is not necessarily a guide to future performance. Forward-looking information or statements in this report contain information that is based on assumptions, forecasts of future results, estimates of amounts not yet determinable, and therefore involve known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of their subject matter to be materially different from current expectations. 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 (ie 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. To the maximum extent permitted by law, Edison, its affiliates and contractors, and their respective directors, officers and employees will not be liable for any loss or damage arising as a result of reliance being placed on any of the information contained in this report and do not guarantee the returns on investments in the products discussed in this publication. 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.

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

295 Madison Avenue, 18th Floor

10017, New York

US

Sydney +61 (0)2 8249 8342

Level 12, Office 1205

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

295 Madison Avenue, 18th Floor

10017, New York

US

Sydney +61 (0)2 8249 8342

Level 12, Office 1205

95 Pitt Street, Sydney

NSW 2000, Australia

Edison is an investment research and advisory company, with offices in North America, Europe, the Middle East and AsiaPac. The heart of Edison is our world-renowned equity research platform and deep multi-sector expertise. At Edison Investment Research, our research is widely read by international investors, advisers and stakeholders. Edison Advisors leverages our core research platform to provide differentiated services including investor relations and strategic consulting. Edison is authorised and regulated by the Financial Conduct Authority. Edison Investment Research (NZ) Limited (Edison NZ) is the New Zealand subsidiary of Edison. Edison NZ is registered on the New Zealand Financial Service Providers Register (FSP number 247505) and is registered to provide wholesale and/or generic financial adviser services only. Edison Investment Research Inc (Edison US) is the US subsidiary of Edison and is regulated by the Securities and Exchange Commission. Edison Investment Research Limited (Edison Aus) [46085869] is the Australian subsidiary of Edison. Edison Germany is a branch entity of Edison Investment Research Limited [4794244]. www.edisongroup.com

DISCLAIMER
Copyright 2018 Edison Investment Research Limited. All rights reserved. This report has been commissioned by Immutep and prepared and issued by Edison for publication globally. All information used in the publication of this report has been compiled from publicly available sources that are believed to be reliable, however we do not guarantee the accuracy or completeness of this report. Opinions contained in this report represent those of the research department of Edison at the time of publication. The securities described in the Investment Research may not be eligible for sale in all jurisdictions or to certain categories of investors.
This research is issued in Australia by Edison Investment Research Pty Ltd (Corporate Authorised Representative (1252501) of Myonlineadvisers Pty Ltd (AFSL: 427484)) and any access to it, is intended only for "wholesale clients" within the meaning of the Corporations Act 2001 of Australia. The Investment Research is distributed in the United States by Edison US to major US institutional investors only. Edison US is registered as an investment adviser with the Securities and Exchange Commission. Edison US relies upon the "publishers' exclusion" from the definition of investment adviser under Section 202(a)(11) of the Investment Advisers Act of 1940 and corresponding state securities laws. As such, Edison does not offer or provide personalised advice. We publish information about companies in which we believe our readers may be interested and this information reflects our sincere opinions. The information that we provide or that is derived from our website is not intended to be, and should not be construed in any manner whatsoever as, personalised advice. Also, our website and 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 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. This document is provided for information purposes only and should not be construed as an offer or solicitation for investment in any securities mentioned or in the topic of this document. A marketing communication under FCA Rules, this document has not been prepared in accordance with the legal requirements designed to promote the independence of investment research and is not subject to any prohibition on dealing ahead of the dissemination of investment research. Edison has a restrictive policy relating to personal dealing. 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. Edison or its affiliates may perform services or solicit business from any of the companies mentioned in this report. The value of securities mentioned in this report can fall as well as rise and are subject to large and sudden swings. In addition it may be difficult or not possible to buy, sell or obtain accurate information about the value of securities mentioned in this report. Past performance is not necessarily a guide to future performance. Forward-looking information or statements in this report contain information that is based on assumptions, forecasts of future results, estimates of amounts not yet determinable, and therefore involve known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of their subject matter to be materially different from current expectations. 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 (ie 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. To the maximum extent permitted by law, Edison, its affiliates and contractors, and their respective directors, officers and employees will not be liable for any loss or damage arising as a result of reliance being placed on any of the information contained in this report and do not guarantee the returns on investments in the products discussed in this publication. 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.

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

295 Madison Avenue, 18th Floor

10017, New York

US

Sydney +61 (0)2 8249 8342

Level 12, Office 1205

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

295 Madison Avenue, 18th Floor

10017, New York

US

Sydney +61 (0)2 8249 8342

Level 12, Office 1205

95 Pitt Street, Sydney

NSW 2000, Australia

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