A new regulatory strategy for dovitinib

Oncology Venture 9 April 2019 Update
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Oncology Venture

A new regulatory strategy for dovitinib

Clinical update

Pharma & biotech

9 April 2019

Price

SEK6.24

Market cap

SEK314m

US$0.16/DKK; US$0.11/SEK

Net debt (SEKm) at 31 December 2018

24.6

Shares in issue

50.3m

Free float

70%

Code

OV

Primary exchange

NASDAQ First North Stockholm

Secondary exchange

N/A

Share price performance

%

1m

3m

12m

Abs

9.1

(21.8)

(36.1)

Rel (local)

4.3

(30.0)

(41.6)

52-week high/low

SEK15.0

SEK4.3

Business description

Oncology Venture is a Denmark-based biopharmaceutical company focused on oncology. Its patent-protected mRNA-based drug response predictor platform enables the identification of patients with gene expression highly likely to respond to treatment. To date, the company has in-licensed six drug candidates with the intent to conduct focused Phase II clinical trials and then out-license the revamped drugs.

Next events

Initiate 2X-121 Phase II in ovarian cancer

H119

LiPlaCis IND/IDE application approval

H119

Phase II LiPlaCis trial top-line data

H119

Analysts

Nathaniel Calloway

+1 646 653 7036

Briana Warschun

+1 646 653 7031

Oncology Venture is a research client of Edison Investment Research Limited

Oncology Venture (OV) recently revealed its new regulatory strategy and clinical development plan for one of highest priority assets: dovitinib. OV will seek marketing approval for dovitinib based on prior data from Novartis demonstrating non-inferiority versus Nexavar (sorafenib, Bayer) for metastatic renal cell carcinoma (mRCC). Moreover, the company plans to run clinical trials utilising the new drug response predictor (DRP) for the combination of dovitinib + PD-1/PD-L1 to identify mRCC patients highly likely to respond and file a supplemental new drug application (sNDA).

Year end

Revenue (DKKm)

PBT*
(DKKm)

EPS*
(DKK)

DPS
(DKK)

P/E
(x)

Yield
(%)

12/17

5.1

(31.0)

(1.27)

0.0

N/A

N/A

12/18

2.1

(22.5)

(0.44)

0.0

N/A

N/A

12/19e

3.6

(208.6)

(3.87)

0.0

N/A

N/A

12/20e

3.6

(92.5)

(1.63)

0.0

N/A

N/A

Note: *PBT and EPS are normalised, excluding amortisation of acquired intangibles, exceptional items and share-based payments.

Seeking marketing approval via non-inferiority

OV recently announced its plans to submit a new drug application (NDA) to the US FDA for marketing approval of dovitinib, which was in-licensed from Novartis, based on non-inferiority using Novartis’s existing comparator data versus Nexavar for the treatment of mRCC. The company’s ultimate goal is to obtain the NDA, presumably with minimal upfront investment, to potentially streamline a future approval for the drug using its combination DRP (combining dovitinib + PD-1/PD-L1).

A new DRP biomarker – dovitinib + PD-1/PD-L1

OV announced it is developing a new combination dovitinib + PD-1/PD-L1 DRP biomarker to identify mRCC patients highly likely to respond to this treatment regimen. This will require OV to find a partner equipped with a PD-1/PD-L1 asset. OV and its partner will need to run at least a Phase Ib/II and a Phase III trial before filing an sNDA on this proposed combination.

Exploring a potential new asset to in-license

OV is separately investigating an option to in-license the European rights to Ixempra (ixabepilone) from R-Pharm. Ixempra is a chemotherapy approved in the US for metastatic breast cancer (mBC), but is not approved in Europe. OV intends to evaluate Ixempra with its DRP in European clinical trials in patients with mBC and, if these data are positive, OV will have the option to in-license European commercial rights exclusively.

Valuation: SEK1,163.9m or SEK23.13 per share

We have increased our valuation of OV to SEK1,163.9m or SEK23.13 per share (SEK21.71 per diluted share) from SEK1,117.7m or SEK22.22 per share (SEK20.84 per diluted share), primarily driven by our changes to the dovitinib development programme to reflect OV’s new regulatory strategy. We may include the Ixempra programme in our valuation if it enters the clinic in human trials.

Revealing the regulatory strategy for dovitinib

On 3 April 2019, OV announced its new regulatory strategy for dovitinib. The company plans to submit an NDA to the US FDA for marketing approval of dovitinib based on existing Novartis data. The company’s ultimate goal is to obtain marketing approval, presumably with minimal upfront investment, to potentially streamline approval for the combination (dovitinib + PD-1/PD-L1). OV in-licensed dovitinib, an oral tyrosine-kinase inhibitor (TKI) that inhibits several different growth factors (fibroblast growth factor, vascular endothelial growth factor, and platelet-derived growth factor receptors) from Novartis in January 2018. As part of the agreement, OV also received an ample amount of biopsy and gene expression data from previous studies by Novartis.

OV plans to submit the NDA for marketing approval on the basis of existing non-inferiority data versus Nexavar (sorafenib, Bayer) for the treatment of mRCC. This NDA will not include the DRP. Given that there are already well established TKIs established as the standard of care in mRCC (Nexavar and Sutent [sunitinib, Pfizer]), and OV lacks a commercial infrastructure, we do not expect any revenue to be generated solely from this NDA approval. The established competition in this space was likely a motivating factor for the initial divestment of the asset from Novartis. However, the drug did demonstrate clinical activity similar to Nexavar in clinical trials. In the randomised open-label Phase III study, patients with metastatic RCC who previously received one VEGF-targeted therapy and one previous mTOR inhibitor, were given either dovitinib (500mg orally, five days on, two days off schedule) or Nexavar (400mg orally 2x daily). Of the 570 patients included in the trial, 284 patients received dovitinib treatment, while the remaining 286 patients received Nexavar. The median progression-free survival was 3.7 months in the dovitinib group versus 3.6 months in the Nexavar group (p=0.063).1 Moreover, median overall survival was 11.1 months versus 11.0 months in those who received dovitinib and Nexavar, respectively. Adverse events were also similar in both treatment arms including fatigue and hypertension. Although dovitinib demonstrated clinical activity, Novartis ceased its development because it did not show efficacy or safety benefit over Nexavar.

  Motzer, R. J., et al. (2014). Dovitinib versus sorafenib for third-line targeted treatment of patients with metastatic renal cell carcinoma: an open-label, randomised Phase III trial. The Lancet Oncology, 15(3), 286- 296.

Accordingly, OV received positive feedback from FDA biostatisticians to move forward with building out the pre-NDA documents based on these data. The company hopes that marketing approval for dovitinib in mRCC on the basis of non-inferiority will pave the way for sNDAs for dovitinib in combination with a PD-1/PD-L1 and its unique DRP biomarker. It is important to note that although the clinical data are clear, there are remaining uncertainties around this application and the strategy of using prior data has not been vetted. If the NDA is approved, an sNDA for consecutive trials may require smaller clinical trials. However, if the original dovitinib NDA is not approved, the company may move forward with the dovitinib + PD-1/PD-L1 combination programme via a new NDA pathway and may require more time and more patients to fulfil NDA requirements.

A new combination dovitinib + PD-1/PD-L1 DRP biomarker

In April 2019, OV announced the completion of its latest DRP biomarker for the combination of dovitinib + PD-1/PD-L1. We note this is the company’s first mention of its new combination DRP. Since in-licensing dovitinib from Novartis, OV has previously completed its data-mining process for dovitinib and its unique DRP for two distinct indications: renal cancer and endometrial cancer. Optimising the DRP is important for identifying the patients most likely to respond and is an essential step in OV’s business model.

PD-1/PD-L1s, which are immune checkpoint inhibitors, are an emerging standard of care for RCC, among other cancers. Therefore, OV must be able to work within this regimen. For example, Opdivo (nivolumab, Bristol-Myers Squibb) was first approved in 2014 for the treatment of unresectable metastatic melanoma. Since then, the FDA has approved Opdivo for the treatment of roughly 10 additional indications including advanced RCC in patients who have received prior anti-angiogenic therapy.

TKI and PD-1/PD-L1 combination therapy is currently being investigated by several notable pharmaceutical companies, for example, the combination of Lenvima (lenvatinib, Eisai) and Keytruda (pembrolizumab, Merck) for metastatic clear cell RCC. Lenvima, a TKI, in combination with everolimus (a chemotherapy) is approved for the treatment of second-line advanced RCC. Top-line data from the open-label Phase Ib/II trial were presented at the 2018 American Society of Clinical Oncology (ASCO). The Phase III trial of Lenvima + Keytruda and Lenvima + everolimus (chemotherapy) versus Sutent (sunitinib, Pfizer) for the first-line treatment of advanced RCC is ongoing. Similarly, top-line data from the Phase III trial (Javelin Renal 101) of Bavencio (avelumab, Pfizer), a PD-L1, + Inlyta (axitinib, Pfizer), a TKI, versus Sutent as first-line treatment of advanced RCC were presented at the 2018 European Society for Medical Oncology (ESMO) Congress (Exhibit 1).2 Overall survival data were not presented as the data set was not yet complete.

  Motzer RJ, Penkov K, Hannen JBAG, et al. JAVELIN Renal 101: a randomized, Phase III study of avelumab + axitinib vs sunitinib as first-line treatment of advanced renal cell carcinoma (aRCC). In: Proceedings from the 2018 ESMO Congress; October 19-23, 2018; Munich, Germany. 

Exhibit 1: Javelin Renal 101 top-line data

Bavencio (10mg/kg IV every two weeks) +
Inlyta (5mg orally twice daily) (n=442)

Sutent (50mg orally, once per day, 4 weeks on and two weeks off) (n=444)

Median PFS (months)

13.8

8.4

ORR (%)

51

26

Source: Motzer et al.2

OV intends to utilise its new combination PD1/PD-L1 and dovitinib DRP biomarker to identify mRCC patients highly likely to respond to this treatment regimen. However, in order to run these trials successfully, OV will need to partner with a PD-1/PD-L1 manufacturer. We assume OV and its future PD-1/PD-L1 partner(s) will be required to run at least a Phase Ib/II trial followed by a Phase III trial, most likely in patients with mRCC receiving second-line therapy. The National Cancer Institute estimates that 63,990 patients in the US were diagnosed with RCC in 2017, or 3.9 per 100,000 men and women on an age-adjusted basis. Roughly 61%3 of RCC patients experience metastatic disease, while 27%4 of those with mRCC require second-line therapy.

  Bianchi, M., et al. (2011). Distribution of metastatic sites in renal cell carcinoma: A population-based analysis. Annals of Oncology, 23(4), 973-980.

  Ko, J. J., et al . (2014). First-, second-, third-line therapy for mRCC: Benchmarks for trial design from the IMDC. British Journal of Cancer, 110(8), 1917-1922.

If the dovitinib standalone NDA is accepted, OV intends to file an sNDA for the combination of dovitinib and a PD-1/PD-L1 in patients with metastatic RCC identified by its unique dovitinib + PD-1/PD-L1 DRP biomarker considered highly likely to respond. However, if the original dovitinib NDA is not approved, the company may move forward with the dovitinib + PD-1/PD-L1 combination programme, which will require a new NDA. This route may require more time and more patients to fulfil NDA requirements.

Considering a new asset to in-license for mBC

On 4 April 2019, OV announced that it had obtained an option to in-license the European rights to Ixempra (ixabepilone) from R-Pharm, which previously acquired Ixempra from Bristol-Myers Squibb in 2015. Ixempra is a chemotherapy that received FDA approval in 2007 (and 18 other markets worldwide) for the treatment of metastatic or locally advanced breast cancer whose tumours are resistant/ refectory to anthracyclines, taxanes and capecitabine. However, Ixempra is not approved by the European Medicines Agency (EMA). Bristol-Myers Squibb withdrew its marketing authorisation application in 2009 following negative feedback regarding safety, specifically the number of patients developing severe neuropathy, from the EMA Committee for Medicinal Products for Human Use (CHMP).

Based on previous treatment results and tumour gene data published by Bristol-Myers Squibb, OV has evaluated the potential ability of its DRP to identify the patients most likely to benefit from Ixempra therapy. According to the agreement, OV will evaluate Ixempra with its DRP in new European clinical trials in patients with mBC and, if these results are positive, OV will have the option to exclusively in-license European commercial rights. The financial terms of this agreement have not yet been disclosed. According to the company, the inclusion of this programme will not increase its cost base as the clinical development will be financed through a joint venture offering to interested investors. Note that we do not include the Ixempra programme in our valuation of OV at this time, although we may add it later if the joint venture advances and the drug enters the clinic.

Women’s cancer initiative

OV also recently announced its collaboration with the German NOGGO and the Danish Breast Cancer Group (DBCG). The German NOGGO and DBCG organisations are responsible for bringing together health professionals focused on improving women’s health and organising all Danish hospitals treating breast cancer patients, respectively. The goal of this collaboration is to accelerate the speed of patient inclusion in OV’s clinical trials. According to OV, collaboration with the German NOGGO includes the activation of four clinical sites in Germany in OV’s two ovarian cancer trials including 2X-121 and Irofulven, as well as three breast cancer trials including LiPlaCis, 2X-121, and 2X-111.

Valuation

We have increased our valuation of OV to SEK1,163.9m or SEK23.13 per share (SEK21.71 per diluted share) from SEK1,117.7m or SEK22.22 per share (SEK20.84 per diluted share). This increase is primarily driven by our changes to the dovitinib development programme to reflect OV’s new regulatory strategy.

We assign a 50% probability of NDA approval of dovitinib for metastatic RCC using existing Novartis data. Although the clinical data for non-inferiority are clear, there are remaining uncertainties around this application and the strategy of using prior data has not been vetted. For the purpose of this scenario, we model costs of ~US$3.4m attributed with the NDA filing and additional overhead. Moreover, we do not foresee sales of dovitinib from the original NDA.

Provided that the NDA is approved, we expect the company to partner with a PD-1/PD-L1 manufacturer, and subsequently run a Phase Ib/II and a Phase III trial investigating dovitinib + PD-1/PD-L1 combination therapy utilising the unique DRP biomarker for the treatment of second-line mRCC. If these data are positive, the company will submit an sNDA for dovitinib, which may entail either a regular or accelerated approval. This is determined on a case-by-case basis. The sNDA will require the same quality content as the original NDA, although the trial can be smaller. Historically, secondary TKI approvals may utilise roughly 30% fewer patients. Moreover, the application will require a full safety profile in the population as well as comparisons with previously approved indications.

Scenario 1: If the NDA is approved based on existing non-inferiority data, we assume that the sNDA for dovitinib in combination with the PD-1/PD-L1 using the DRP has a probability of approval of 50%. Via the sNDA regulatory pathway, we assume launch in 2024 and peak sales of US$193.1m.

However, if the original dovitinib NDA is not approved, the company may move forward with the dovitinib + PD-1/PD-L1 combination programme, which will require a new NDA. This route may require more time and more patients to fulfil NDA requirements.

Scenario 2: If the NDA is not approved based on existing non-inferiority data, we assume the new NDA for dovitinib in combination with the PD-1/PD-L1 using the DRP has a probability of approval of 35%. Via the new NDA regulatory pathway, we assume launch in 2025 and peak sales of $191.8m.

We have calculated an expectation value of dovitinib based on these assumptions, which includes the probability of approval of these events. To model this, we utilise a decision tree which illustrates several possible scenarios (Exhibit 2).

Exhibit 2: Expectation value of dovitinib in RCC

Step 1

Value/cost ($m)

Decision

Prob.

Step 2

Decision

Prob.

NPV for stage
($m)

Total adjusted NPV*
($m)

NDA Novartis non-inferiority data

(3.4)

Approved

50%

sNDA pathway

Approved

50%

82.4

39.5

Not approved

50%

0

(0.26)

Not approved

50%

New NDA pathway

Approved

35%

49.8

23.2

Not approved

65%

0

(0.43)

Total value of dovitinib programme

62.0

Source: Edison Investment Research. Notes: NDA= new drug application; sNDA= supplemental new drug application. *Total adjusted NPV represents the residual value of revenue and costs of the scenario after adjusting for its probability.

Our new valuation of the dovitinib programme based on this analysis is SEK565.0m (US$62.0m) or SEK310.8m as per OV’s 55% ownership of the asset. Our previous valuation of the dovitinib programme (SEK264.5m as per OV’s 55% stake in the asset) was based on third-line metastatic RCC and liver cancer as per previous guidance from the company. We may add the Ixempra programme to our valuation if it enters the clinic in human trials.

Exhibit 3: Valuation of OV

Development programme

Indication

Clinical stage

Prob. of success

Launch year

Launch pricing

Peak sales ($m)

rNPV (SEKm)

% owned by OV

OV rNPV (SEKm)

LiPlaCis

Metastatic breast cancer and metastatic prostate cancer

Phase II

25%

2023

$91,000

259.8

695.3

39%

271.2

Irofulven

Metastatic prostate cancer

Phase Ib/II

20%

2023

$129,000

52.6

61.9

100%

61.9

APO010

Multiple myeloma

Phase Ib/II

20%

2023

$143,000

80.9

101.1

100%

101.1

2X-121

Metastatic breast cancer and ovarian cancer

Phase II

25%

2023

$132,000

116.4

180.0

92%

165.6

2X-111

Glioblastoma and brain metastases from breast cancer

Phase Ib/II

25%

2024

$169,000

212.6

302.3

92%

278.2

Dovitinib

Renal cancer

Phase Ib/II

35–50%

2024–25

$145,000

157.2–158.3

565.0

55%

310.8

Total

 

 

 

 

 

 

 

 

1,188.6

Net debt (at 31 December 2018) (SEKm)

(24.6)

Total firm value (SEKm)

1,163.9

Total shares (m)

50.3

Value per basic share (SEK)

23.13

Warrants and options (m)

3.3

Fully diluted shares in issue (m)

53.6

Fully diluted value per share (SEK)

21.71

Source: Oncology Venture reports, Edison Investment Research

Financials

We have adjusted our financial forecasts to reflect the new development strategy for dovitinib. While our 2019 operating cash burn estimate has increased from DKK197.1m to DKK212.4m, our total estimates of future financial obligations remain unchanged at DKK388m because they reflect the cost to bring all six assets to the partnering stage (through Phase II trials). However we acknowledge that de-risking of dovitinib through the current strategy will increase its value to future partners. On 5 April 2019, OV announced an ongoing rights offering, which includes up to 25.2m units of one share and one warrant exercisable at SEK7.50 at the price of SEK4.00 per unit. The subscription period will begin on 17 April 2019 and run through 2 May 2019. We assume that all six of OV’s assets will move forward; however, costs may be brought down if the development programmes do not progress as we expect.

Exhibit 4: Financial summary

DKK000s

2017

2018

2019e

2020e

Year end 31 December

IFRS

IFRS

IFRS

IFRS

PROFIT & LOSS

Revenue

 

 

 

5,145

2,147

3,646

3,646

Cost of Sales

0

0

0

0

Gross Profit

5,145

2,147

3,646

3,646

EBITDA

 

 

 

(23,794)

(32,258)

(206,802)

(92,500)

Operating Profit (before amort. and except.)

 

 

 

(23,848)

(32,471)

(206,589)

(92,287)

Intangible Amortisation

0

0

0

0

Exceptionals/Other

0

0

0

0

Operating Profit

(23,848)

(32,471)

(206,589)

(92,287)

Net Interest

(7,132)

(192)

(2,015)

(212)

Other

0

10,146

0

0

Profit Before Tax (norm)

 

 

 

(30,980)

(22,517)

(208,604)

(92,499)

Profit Before Tax (IFRS)

 

 

 

(30,980)

(22,517)

(208,604)

(92,499)

Tax

590

6,973

3,999

1,822

Deferred tax

0

0

0

0

Profit After Tax (norm)

(30,390)

(15,544)

(204,604)

(90,677)

Profit After Tax (IFRS)

(30,390)

(15,544)

(204,604)

(90,677)

Average Number of Shares Outstanding (m)

24.3

33.8

52.8

55.5

EPS - normalised (DKK)

 

 

 

(1.27)

(0.44)

(3.87)

(1.63)

EPS - IFRS (DKK)

 

 

 

(1.27)

(0.44)

(3.87)

(1.63)

Dividend per share (ore)

0.0

0.0

0.0

0.0

BALANCE SHEET

Fixed Assets

 

 

 

4,883

237,096

237,096

237,096

Intangible Assets

135

236,733

236,733

236,733

Tangible Assets

4,424

363

363

363

Other

324

0

0

0

Current Assets

 

 

 

8,102

14,401

33,161

99,275

Stocks

1,048

0

0

0

Debtors

3,048

5,262

20,660

9,414

Cash

3,326

1,547

910

76,447

Other

680

7,592

11,591

13,413

Current Liabilities

 

 

 

(10,540)

(35,407)

(29,263)

(13,241)

Creditors

(10,540)

(16,515)

(29,263)

(13,241)

Short term borrowings

0

(18,892)

0

0

Long Term Liabilities

 

 

 

0

(34,234)

(265,126)

(441,126)

Long term borrowings

0

0

(230,892)

(406,892)

Other long term liabilities

0

(34,234)

(34,234)

(34,234)

Net Assets

 

 

 

2,445

181,856

(24,132)

(117,996)

CASH FLOW

Operating Cash Flow

 

 

 

(10,702)

(31,392)

(212,424)

(100,250)

Net Interest

(170)

(2,391)

0

0

Tax

2,527

6,159

0

0

Capex

0

0

(213)

(213)

Acquisitions/disposals

(784)

9,855

0

0

Financing

7,478

198

0

0

Dividends

0

0

0

0

Other

(308)

(3,299)

0

(102)

Net Cash Flow

(1,959)

(20,870)

(212,637)

(100,565)

Opening net debt/(cash)

 

 

 

(5,488)

(3,326)

17,345

229,982

HP finance leases initiated

0

0

0

0

Exchange rate movements

(203)

(199)

0

0

Other

0

398

0

0

Closing net debt/(cash)

 

 

 

(3,326)

17,345

229,982

330,547

Source: Oncology Venture reports, Edison Investment Research.

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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).

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United States

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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

The Investment Research is a publication distributed in the United States by Edison Investment Research, Inc. Edison Investment Research, Inc. is registered as an investment adviser with the Securities and Exchange Commission. Edison 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. This report is a bona fide publication of general and regular circulation offering impersonal investment-related advice, not tailored to a specific investment portfolio or the needs of current and/or prospective subscribers. As such, Edison does not offer or provide personal advice and the research provided is for informational purposes only. No mention of a particular security in this report constitutes a recommendation to buy, sell or hold that or any security, or that any particular security, portfolio of securities, transaction or investment strategy is suitable for any specific person.

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

1,185 Avenue of the Americas

3rd Floor, New York, NY 10036

United States of America

Sydney +61 (0)2 8249 8342

Level 4, Office 1205

95 Pitt Street, Sydney

NSW 2000, Australia

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