International Stem Cell — Green light for second cohort

International Stem Cell — Green light for second cohort

International Stem Cell recently announced that the data safety monitoring board (DSMB) for its Phase I trial of ISC-hpNSC in Parkinson’s disease (PD) has authorized the enrollment of the second cohort of four patients. The study will ultimately enroll 12 patients at three dosing regimens (30m-70m cells) with a primary endpoint of safety, but will provide preliminary efficacy data measured at six and 12 months following the treatment.

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Written by

International Stem Cell

Green light for second cohort

Development update

Pharma & biotech

24 May 2017

Price

US$1.50

Market cap

US$6m

Net cash ($m) at 31 March 2017

0.7

Shares in issue

4.0m

Free float

46.8%

Code

ISCO

Primary exchange

OTC

Secondary exchange

N/A

Share price performance

%

1m

3m

12m

Abs

(14.3)

11.1

(31.8)

Rel (local)

(16.1)

9.5

(41.8)

52-week high/low

US$2.3

US$0.9

Business description

International Stem Cell is an early-stage biotechnology company developing therapeutic, biomedical and cosmeceutical applications for its proprietary stem form of pluripotent stem cells – human parthenogenetic stem cells (hpSCs). Its lead candidate is a cell therapy treatment for Parkinson’s disease.

Next events

Initial efficacy data from first cohort

Q317

Initiation of Phase II in traumatic brain injury

Q317

Analysts

Maxim Jacobs

+1 646 653 7027

Nathaniel Calloway

+1 646 653 7036

International Stem Cell is a research client of Edison Investment Research Limited

International Stem Cell recently announced that the data safety monitoring board (DSMB) for its Phase I trial of ISC-hpNSC in Parkinson’s disease (PD) has authorized the enrollment of the second cohort of four patients. The study will ultimately enroll 12 patients at three dosing regimens (30m-70m cells) with a primary endpoint of safety, but will provide preliminary efficacy data measured at six and 12 months following the treatment.

Year
end

Revenue ($m)

PBT*
($m)

EPS*
($)

DPS
($)

P/E
(x)

Yield
(%)

12/15

7.6

(4.6)

(1.29)

0.0

N/A

N/A

12/16

7.2

(4.9)

(0.34)

0.0

N/A

N/A

12/17e

7.6

(4.9)

(1.22)

0.0

N/A

N/A

12/18e

8.3

(8.2)

(1.96)

0.0

N/A

N/A

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

Trial in Parkinson’s disease continuing

Patients on the study will be treated in three cohorts with 30m, 50m and 70m stem cells, delivered via intracranial injection. The single-arm, open-label study is being conducted at the Royal Melbourne Hospital in Australia. Clinical assessments are scheduled at six and 12 months following surgery. The data from this trial will be used in the design of a future Phase II trial, which is expected to initiate in late 2017 or early 2018.

Early efficacy data in Q317

Besides safety, the trial will also provide physiological and functional assessments of the patients, which will give the first indication of the efficacy of the treatment in humans. Brain function will be directly assessed via PET scan to assess the degree of disease progression. Additionally, patients will be assessed via the six-point Unified Parkinson’s Disease Rating Scale (UPDRS), a qualitative functional scale of a patient’s mental state, muscle tone and ability to perform daily tasks. We expect to see some early efficacy data from the first cohort of patients in Q317.

Traumatic brain injury Phase II coming soon

The company is preparing to initiate a Phase II study of ISC-hpNSC in traumatic brain injury (TBI). According to the Centers for Disease Control, TBI accounts for 2.5m emergency room visits in the US annually and approximately 3.2-5.3m people are living with a TBI-related disability.

Valuation: $27m or $6.62 per basic share

We have updated our valuation to $27m or $6.62 per basic share from $28m or $6.97/share. The difference is mainly due to lower net cash and a higher share count. There remain approximately 14.2m potentially dilutive shares from warrants, options and convertible preferred stock. We project that the company will need at least $70m in additional financing before profitability in 2024, of which $7.5m will be required by the end of 2017. However, if it continues its cost controls (the company only burned $190,000 per month in Q117), this estimate may be lower in the future.

ISC-hpNSC for Parkinson’s disease

International Stem Cell Corporation has announced that the DSMB has approved the enrollment of the second cohort of four patients into its Phase I trial in Parkinson’s disease (PD). It had initiated the Phase I trial of ISC-hpNSC for the treatment of PD in July 2016. ISC-hpNSC are the company’s proprietary neural stem cells (NSC) derived from a human parthenogenetic stem cell line (hpSC). The trial is a dose escalation study designed to evaluate the safety of the intracranial injection of 30m, 50m and 70m cells. The trial is also evaluating the treatment for efficacy by monitoring changes in brain function via PET scan, as well as functional assessment via the UPDRS over the course of 12 months.

The UPDRS is the most common standardized assessment used to monitor the progression and severity of PD in the clinical setting. It comprises six sections, including both patient and clinician evaluation of motor function, mood and the ability to perform daily tasks (Exhibit 1).

Exhibit 1: Unified Parkinson’s Disease Rating Scale

Section

Description

Assessments

1

Mental assessment

Intellectual impairment, thought disorder, depression and initiative

2

Patient scored evaluation of ability to perform daily activities

Hygiene, food preparation, dressing, avoiding falls, speech, tremor etc

3

Clinician scored motor assessment

Measures of function (tremor, rigidity, posture), functional assessments (ability to rise from a chair, gait, speech) and evaluation of specific muscle groups (fingers, face, legs)

4

Complications associated with therapy

Rate of dyskinesia, assessments of “off” periods, other complications of treatment (nausea, insomnia, etc)

5

The Modified Hoehn Yahr Staging

Global evaluation ranging from no visible signs of disease to wheelchair-bound state

6

Schwab & England Activities of Daily Living Scale

Degree of independence from care givers ranging from completely independent to inability to swallow or perform bowel movements

Source: National Parkinson Foundation

The study is being performed at the Royal Melbourne Hospital in Australia and has a targeted enrollment of 12 moderate to severe PD patients. We expect to see some early efficacy data from the first cohort of patients in Q317.

PD affects 7-10m people worldwide, with approximately 1.5m in the US. The most widespread treatment for the disease is the combination of levodopa and carbidopa, which provides the brain with dopamine lost by the death of dopaminergic neurons. The majority of clinical development in the space has been focused on the reformulation of this and other treatment regimens and, to date, no disease-modifying therapies have been approved.

Traumatic brain injury Phase II planned

The company recently announced plans to start a Phase II study of ISC-hpNSC for the treatment of traumatic brain injury (TBI) following preclinical results in rodents suggesting the therapy can improve cognitive performance and motor co-ordination in those with the condition. We expect the company to conduct the Phase II trial in Australia where it would only need Ethics Committee approval to start the trial. Also, once Phase II data are in hand, we would expect the company to apply to the FDA for the new Regenerative Medicine Advanced Therapy (RMAT) designation, which came into existence as part of the 21st Century Cures Act. Sponsors of regenerative medicine products, like ISC-hpNSC, may obtain the designation if the drug is intended to treat a serious or life-threatening condition and there is some preliminary clinical evidence of the ability to address unmet medical needs for that condition. RMAT designation allows for increased interactions with the FDA, similar to the interactions available to those with breakthrough designation, and the company may also become eligible for priority review and accelerated approval.

According to the Centers for Disease Control, TBI accounts for 2.5m emergency room visits in the US annually and approximately 3.2-5.3m people are living with a TBI-related disability with no effective long-term treatments outside of rehabilitation. Given the size, TBI could be as meaningful to the company as PD, for which we currently forecast $2.8bn in peak sales. We expect the company to report on a dose-escalating animal study in the coming months and initiate the Phase II study in Q317.

Valuation

We have updated our valuation to $27m or $6.62 per basic share from $28m or $6.97 per basic share. The difference is mainly due to a lower net cash level and a higher share count. There remain approximately 14.2m potentially dilutive shares from warrants, options and convertible preferred stock.

Exhibit 2: Risk-adjusted NPV valuation model

Product

Status

Launch

Peak sales ($m)

NPV ($m)

Probability (%)

rNPV ($m)

NPV/share ($)

Cosmetic and biomedical business

Commercial

Current

18

23

90%

21

5.21

Parkinson’s disease (royalties at 12% of sales)

Phase I/IIa

2024

2,800

467

7.5%

35

8.74

G&A expense - after tax

100%

(29)

(7.17)

Net cash

(0.7)

100%

(0.7)

(0.16)

Valuation

 

 

 

489

 

27

6.62

Source: Edison Investment Research estimates

Financials

International Stem Cell reported Q117 revenues of $2.0m, up 24.1% compared to Q116. The biomedical business continues to grow with revenues of $1.4m, up 65.1% compared to last year, but the cosmetics business was down 21.8%. For the company as a whole, the operating loss was $1.0m for the quarter. We have adjusted our model to reflect stronger biomedical sales and weaker cosmetic sales than we had forecast as well as slightly lower R&D expenses. The company reported $676,000 in cash and burned $571,000 in cash last quarter.

Exhibit 3: Changes to estimates

$000s

Revenue

Operating profit

Profit after tax

Old

New

% change

Old

New

% change

Old

New

% change

2017e

7,593

7,601

0.1%

(5,290)

(4,286)

19.0%

(5,890)

(4,886)

17.0%

2018e

8,341

8,343

0.1%

(6,958)

(6,957)

0.0%

(8,158)

(8,157)

0.0%

Source: Edison Investment Research. Note: Operating profit and profit after tax exclude amortization of acquired intangibles, exceptional items and share-based payments.

We project that the company will need at least $70m in additional financing before profitability in 2024, of which $7.5m will be required by the end of 2017. However, if the company continues its cost controls (it only burned $190,000 per month in Q117), this estimate may be decreased in the future.

Exhibit 4: Financial summary

US$000

2015

2016

2017e

2018e

Year end 31 December

US GAAP

US GAAP

US GAAP

US GAAP

PROFIT & LOSS

Revenue

 

 

7,551

7,165

7,601

8,343

Cost of Sales

(2,056)

(1,944)

(2,052)

(2,169)

Gross Profit

5,495

5,221

5,549

6,174

Research and development

(2,707)

(2,856)

(3,000)

(6,000)

EBITDA

 

 

(5,036)

(5,182)

(4,617)

(7,288)

Operating Profit (before amort. and except.)

(4,564)

(4,851)

(4,286)

(6,957)

Intangible Amortisation

0

0

0

0

Exceptionals

0

0

0

0

Other

1,929

3,772

0

0

Operating Profit

(2,635)

(1,079)

(4,286)

(6,957)

Net Interest

0

0

(600)

(1,200)

Profit Before Tax (norm)

 

 

(4,564)

(4,851)

(4,886)

(8,157)

Profit Before Tax (reported)

 

 

(2,635)

(1,079)

(4,886)

(8,157)

Tax

0

0

0

0

Profit After Tax (norm)

(2,635)

(1,079)

(4,886)

(8,157)

Profit After Tax (reported)

(2,635)

(1,079)

(4,886)

(8,157)

Average Number of Shares Outstanding (m)

2.0

3.2

4.0

4.2

EPS - normalised (US$)

 

 

(1.29)

(0.34)

(1.22)

(1.96)

EPS - normalised fully diluted (US$)

 

 

(1.29)

(0.34)

(1.22)

(1.96)

EPS - (reported) (US$)

 

 

(1.29)

(0.34)

(1.22)

(1.96)

Dividend per share (US$)

0.0

0.0

0.0

0.0

Gross Margin (%)

72.8

72.9

73.0

74.0

EBITDA Margin (%)

N/A

N/A

N/A

N/A

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

N/A

N/A

N/A

N/A

BALANCE SHEET

Fixed Assets

 

 

4,147

4,553

5,087

5,636

Intangible Assets

3,223

3,484

4,032

4,579

Tangible Assets

864

1,011

998

999

Investments

60

58

58

58

Current Assets

 

 

2,991

2,492

5,802

5,675

Stocks

1,348

1,390

1,357

1,489

Debtors

539

574

543

596

Cash

532

110

3,484

3,172

Other

572

418

418

418

Current Liabilities

 

 

(5,544)

(3,601)

(3,859)

(3,967)

Creditors

(5,544)

(3,601)

(3,859)

(3,967)

Short term borrowings

0

0

0

0

Long Term Liabilities

 

 

0

0

(7,500)

(15,000)

Long term borrowings

0

0

(7,500)

(15,000)

Other long term liabilities

0

0

0

0

Net Assets

 

 

1,594

3,444

(470)

(7,655)

CASH FLOW

Operating Cash Flow

 

 

(4,120)

(4,197)

(2,661)

(5,732)

Net Interest

0

0

(600)

(1,200)

Tax

0

0

0

0

Capex

(738)

(944)

(865)

(880)

Acquisitions/disposals

0

0

0

0

Financing

1,169

4,018

0

0

Dividends

0

0

0

0

Net Cash Flow

(3,689)

(1,123)

(4,126)

(7,812)

Opening net debt/(cash)

 

 

(1,111)

(532)

(110)

4,016

HP finance leases initiated

0

0

0

0

Other

3,110

701

0

0

Closing net debt/(cash)

 

 

(532)

(110)

4,016

11,828

Source: Edison Investment Research

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DISCLAIMER
Copyright 2017 Edison Investment Research Limited. All rights reserved. This report has been commissioned by International Stem Cell 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 Aus and any access to it, is intended only for "wholesale clients" within the meaning of the Australian Corporations Act. 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.
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245 Park Avenue, 39th Floor

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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 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 and is not regulated by the Australian Securities and Investment Commission. Edison Germany is a branch entity of Edison Investment Research Limited [4794244]. www.edisongroup.com

DISCLAIMER
Copyright 2017 Edison Investment Research Limited. All rights reserved. This report has been commissioned by International Stem Cell 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 Aus and any access to it, is intended only for "wholesale clients" within the meaning of the Australian Corporations Act. 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 2017. “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

245 Park Avenue, 39th Floor

10167, 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

245 Park Avenue, 39th Floor

10167, New York

US

Sydney +61 (0)2 8249 8342

Level 12, Office 1205

95 Pitt Street, Sydney

NSW 2000, Australia

Corestate Capital Holding — The investment manufactory

Corestate Capital (CCAP) is an integrated real estate investment manager providing a range of asset management products and services. It focuses on commercial and residential property in Germany, Austria and other European markets, often co-investing with its family office, and institutional and high net worth investor clients. The pending acquisition of Hannover Leasing (HLG) will make it one of the leading real estate fund managers in German-speaking Europe, with AUM of €16bn. No details of the transaction have been disclosed. Even without factoring in the financial impact of the HLG deal, CCAP is trading on a P/E ratio of 17x and yielding nearly 5%.

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