Newron Pharmaceuticals — Evenamide down but not out

Newron Pharmaceuticals (SIX: NWRN)

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Research: Healthcare

Newron Pharmaceuticals — Evenamide down but not out

Newron’s plans for its novel mechanism of action drug, Evenamide, due to enter late-stage development for schizophrenia, have been delayed. Specifically, the FDA has requested that Newron carry out additional short-term safety studies before larger, pivotal-stage clinical trials can be undertaken. This has taken us and the market by surprise, as we had expected the two Phase II/III trials to start in Q219 as per guidance. The delay is a setback and we therefore push back our launch expectations by 18 months to 2024, erring on the side of caution. We now value Newron at CHF653m vs CHF714m previously.

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Healthcare

Newron Pharmaceuticals

Evenamide down but not out

R&D update

Pharma & biotech

31 May 2019

Price

CHF6.37

Market cap

CHF113m

€0.89/CHF; $1.01/CHF; $1.12/€

Net cash (€m) at 31 December 2018

43.9

Shares in issue

17.8m

Free float

95%

Code

NWRN

Primary exchange

SIX

Secondary exchange

N/A

Share price performance

%

1m

3m

12m

Abs

(30.3)

(26.6)

(41.9)

Rel (local)

(28.7)

(27.8)

(47.1)

52-week high/low

CHF13.64

CHF5.41

Business description

Newron Pharmaceuticals is an Italian CNS-focused biotechnology company. Xadago (safinamide) for Parkinson’s disease has been launched in Europe and the US. Xadago is partnered with Zambon (EU), Meiji Seika (Japan), US WorldMeds (US), Seqirus (Australia/New Zealand) and Medison Pharma (Israel).

Next events

Additional FDA feedback on Evenamide Phase IIb/III trial

Mid-2019

Sarizotan Phase III STARS data

Q419

Sarizotan NDA filing

2020

Analysts

Dr Susie Jana

+44 (0)20 3077 5700

Dr Sean Conroy

+44 (0)20 3681 2534

Newron Pharmaceuticals is a research client of Edison Investment Research Limited

Newron's plans for its novel mechanism of action drug, Evenamide, due to enter late-stage development for schizophrenia, have been delayed. Specifically, the FDA has requested that Newron carry out additional short-term safety studies before larger, pivotal-stage clinical trials can be undertaken. This has taken us and the market by surprise, as we had expected the two Phase II/III trials to start in Q219 as per guidance. The delay is a setback and we therefore push back our launch expectations by 18 months to 2024, erring on the side of caution. We now value Newron at CHF653m vs CHF714m previously.

Year end

Revenue (€m)

PBT*
(€m)

EPS*
(€)

DPS
(€)

P/E
(x)

Yield
(%)

12/17

13.4

(5.3)

(0.32)

0.0

N/A

N/A

12/18

4.0

(15.0)

(0.84)

0.0

N/A

N/A

12/19e

8.6

(14.2)

(0.79)

0.0

N/A

N/A

12/20e

21.7

(3.5)

(0.20)

0.0

N/A

N/A

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

Regression to Phase I studies unexpected

The emergence of safety concerns from preclinical models is unexpected given that positive clinical safety data were reported from the Phase I/IIa proof-of-concept study of Evenamide (March 2017). The concerns raised by the FDA related specifically to a chronic toxicity study in rats and CNS events observed in dogs at higher doses, which could be related to a class effect for the drug. Management will meet with the FDA to discuss what is required in more detail, but has indicated that additional preclinical and clinical safety studies (presumably Phase I in healthy volunteers) are likely to be required before a Phase III study is cleared by the regulators. We now estimate that registrational studies will not start until late-2020/early-2021, pushing back a potential launch to early-2024 (from late-2022).

Sarizotan and Xadago development plans on track

Newron remains well funded through key near-term inflections, including top-line data from the pivotal study of sarizotan in Rett syndrome (Q419) and its subsequent regulatory filing (2020), and the start of a label extension study for its commercial Parkinson’s disease (PD) drug Xadago for levodopa-induced dyskinesia (Q319). Newron reported net cash of €43.9m at end December 2018 and has access to an additional €40m loan facility through the European Investment Bank (EIB).

Valuation: CHF653m or CHF36.6/share

Our valuation of Newron has decreased to CHF653m from CHF714m. We have reduced the probability of success for Evenamide to 30% (from 50%), given that it is now likely to require an additional Phase I study, and pushed back its launch to 2024. Our valuation remains heavily skewed to Xadago and sarizotan, which represent 56% and 26% of our rNPV valuation, respectively. Sales of Xadago need to ramp up to reach our peak sales forecast of €679m.

Safety first, safety second

Following the initial announcement, management followed up with an analyst call during which it highlighted that the concerns raised by the US FDA related to recently completed preclinical studies, including recent (undisclosed) findings from a long-term (26-week) toxicology study in rats and undisclosed CNS events observed in dogs on higher doses of Evenamide. These specifically related to Evenamide, as the studies did not relate to any combinations with atypical antipsychotics. Management has guided that these could be associated with commonly observed class effects related to the mechanism of action through which Evenamide works (inhibition of voltage-gated sodium channels). Management has guided that long-term preclinical toxic studies (26 to 52 weeks) are unlikely to be required and that sufficient preclinical safety data can be generated from short-term studies (four to eight weeks). However, the likely requirement to conduct another Phase I clinical study (50–60 healthy volunteers), even in parallel to preclinical work, will significantly affect development timelines; we note that the original Phase I study for Evenamide (conducted in 54 healthy volunteers) took 18 months to complete. With this in mind, we do not anticipate that Newron will be able start the originally proposed registrational studies for 18 months, which takes into account time frames to interact with the FDA, agree an appropriate study plan, analyse data and present the findings. Following receipt of further guidance from the FDA, we will revise these assumptions.

Cross-supportive studies remain the most likely path

Newron had been in active discussions with several regulatory bodies, including an end of Phase II meeting with the US FDA in Q218, to design two cross-supportive Phase IIb/III clinical trials for Evenamide in two schizophrenia patient populations, which Newron had previously expected to start in Q219 and complete in H220.

Study 003/005 for non-treatment resistant patients: chronic schizophrenic patients inadequately responding to atypical antipsychotic monotherapy (risperidone, aripiprazole, paliperidone, olanzapine or quetiapine). This trial will evaluate the efficacy, safety and tolerability of three fixed doses of Evenamide (or placebo) as an add-on to the patient’s current atypical antipsychotic medication.

Study 004/006 for treatment-resistant patients: defined as treatment-resistant schizophrenia (TRS) patients whose psychotic symptoms have failed two or more prior lines of pharmacotherapy and are not adequately responding to clozapine after 12 weeks. This trial will evaluate the efficacy, safety and tolerability of two fixed doses of Evenamide (or placebo) as add-on to clozapine.

We expect that Newron should be back on track to start these pivotal studies once the supportive explanatory studies have been completed. Regulators had indicated that positive results in both 003/005 and 004/006 would be enough to cover the efficacy requirements for submitting an NDA across both indications. If study 003/005 alone is positive, another confirmatory Phase III trial would be needed for this larger patient subset. We note that this scenario would require us to revisit our forecasts.

Exhibit 1: Likely approval pathways following Phase IIb/III studies

Study 003/005
Non-treatment-resistant patients (add-on to any atypical APD)

Negative readout

Positive readout

Study 004/006
Treatment-resistant patients (add-on to clozapine)

Negative readout

No regulatory approval

Confirmatory Phase III trial of similar design

Positive readout

Approval for TRS as an add-on to clozapine (breakthrough designation)

Approval for both treatment-resistant and non-TRS as an add-on to any atypical antipsychotic drug

Source: Edison Investment Research. Note: APD – antipsychotic drug.

As an add-on to atypical antipsychotic drugs (APD) in the wider schizophrenia patient population, the scope for Evenamide is potentially huge and Newron would need to partner for the wider schizophrenia indication (add-on to any APD). However, Newron could elect to market the smaller indication of TRS as defined by resistance to clozapine by itself, and could rapidly capture this smaller subset of patients if breakthrough designation was granted.

Valuation

Our revised valuation of Newron is CHF653m (CHF36.6/share), down 8.5% from our previous valuation of CHF714m (CHF40.1/share) (Exhibits 3 and 4). This downgrade stems from reducing our probability of success for Evenamide to 30% from 50% to reflect the need for additional preclinical and Phase I studies, and delaying potential launch from late-2022 to early-2024. We have pushed back Evenamide-associated R&D to reflect the timing of the start of the larger, more costly Phase II/III programme. Additionally, we have rolled forward our model and updated FX rates. Our valuation includes Xadago peak sales in Parkinson’s disease, in addition to risk-adjusted contributions from Xadago for PD-related levodopa-induced dyskinesia (LID), sarizotan in Rett syndrome (RS) and Evenamide in schizophrenia. The breakdown of our rNPV valuation, using a 12.5% discount rate for clinical-stage assets and a 10% discount rate for commercially available asset Xadago, is shown in Exhibit 2.

Exhibit 2: Newron sum-of-the-parts valuation

Product

Indication

Launch

Peak sales* (€m)

NPV
(€m)

NPV (CHFm)

Probability

rNPV (€m)

rNPV (CHFm)

rNPV/share (CHF/share)

Xadago

Parkinson's disease

2015

679

280.6

314.9

100%

280.6

314.9

17.6

Dyskinesia

2021

358

84.1

94.3

50%

42.2

47.4

2.7

Sarizotan

RS

2021

574

540.8

606.9

30%

152.2

170.8

9.6

Evenamide

Schizophrenia

2024

960

245.3

275.3

30%

62.9

70.5

4.0

Net cash at 31 December 2018

43.9

49.2

100%

43.9

49.2

2.8

Valuation

 

 

 

1,194.6

1,340.6

581.7

652.8

36.6

Source: Edison Investment Research. Note: *FX changes have increased our forecast peak sales slightly.

Exhibit 3: Previous rNPV split

Exhibit 4: Revised rNPV split

Source: Edison Investment Research

Source: Edison Investment Research

Exhibit 3: Previous rNPV split

Source: Edison Investment Research

Exhibit 4: Revised rNPV split

Source: Edison Investment Research

Exhibit 5: Financial summary

€000s

2016

2017

2018

2019e

2020e

Year-end 31 December

IFRS

IFRS

IFRS

IFRS

IFRS

PROFIT & LOSS

Revenue

 

 

6,726

13,428

4,025

8,559

21,689

Cost of Sales

0

0

0

0

0

Gross Profit

6,726

13,428

4,025

8,559

21,689

Research and development (net)

(12,398)

(8,596)

(9,835)

(13,160)

(15,620)

EBITDA

 

 

(15,290)

(4,298)

(14,931)

(14,255)

(3,603)

Operating Profit (before amort. and except.)

 

 

(15,318)

(4,332)

(14,967)

(14,277)

(3,626)

Intangible Amortisation

(7)

(14)

(11)

(24)

(18)

Exceptionals

0

0

0

0

0

Other

0

0

0

0

0

Operating Profit

(15,325)

(4,346)

(14,978)

(14,301)

(3,644)

Net Interest

121

(955)

(41)

111

93

Profit Before Tax (norm)

 

 

(15,197)

(5,287)

(15,008)

(14,166)

(3,533)

Profit Before Tax (reported)

 

 

(15,204)

(5,301)

(15,019)

(14,190)

(3,551)

Tax

(33)

19

(16)

0

0

Profit After Tax (norm)

(15,230)

(5,268)

(15,024)

(14,166)

(3,533)

Profit After Tax (reported)

(15,237)

(5,282)

(15,035)

(14,190)

(3,551)

Average Number of Shares Outstanding (m)

14.7

16.3

17.8

17.8

17.8

EPS - normalised (c)

 

 

(103.69)

(32.32)

(84.20)

(79.39)

(19.80)

EPS - (reported) (€)

 

 

(1.04)

(0.32)

(0.84)

(0.80)

(0.20)

Dividend per share (c)

0.0

0.0

0.0

0.0

0.0

Gross Margin (%)

100.0

100.0

100.0

100.0

100.0

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

 

 

451

224

218

212

211

Intangible Assets

261

35

30

12

0

Tangible Assets

120

107

106

118

129

Investments

70

82

82

82

82

Current Assets

 

 

56,140

72,800

59,512

48,154

47,255

Stocks

5

5

0

0

0

Debtors

9,667

12,714

15,659

15,000

15,000

Cash

46,468

60,081

43,853

33,154

32,255

Other

0

0

0

0

0

Current Liabilities

 

 

(6,645)

(4,727)

(4,281)

(5,000)

(5,544)

Creditors

(6,281)

(4,727)

(4,281)

(5,000)

(5,544)

Short term borrowings

(364)

0

0

0

0

Long Term Liabilities

 

 

(199)

(576)

(606)

(606)

(606)

Long term borrowings

0

0

0

0

0

Other long-term liabilities

(199)

(576)

(606)

(606)

(606)

Net Assets

 

 

49,747

67,721

54,843

42,760

41,317

CASH FLOW

Operating Cash Flow

 

 

(19,616)

(8,404)

(16,108)

(10,770)

(953)

Net Interest

102

388

(3,120)

111

93

Tax

33

0

0

0

0

Capex

(69)

(24)

(34)

(34)

(34)

Acquisitions/disposals

0

0

0

0

0

Financing

25,448

22,324

51

0

0

Other

(3)

(300)

2,983

(6)

(6)

Dividends

0

0

0

0

0

Net Cash Flow

5,895

13,984

(16,228)

(10,699)

(900)

Opening net debt/(cash)

 

 

(40,205)

(46,104)

(60,081)

(43,853)

(33,154)

HP finance leases initiated

0

0

0

0

0

Other

4

(7)

0

0

0

Closing net debt/(cash)

 

 

(46,104)

(60,081)

(43,853)

(33,154)

(32,255)

Source: Company accounts, Edison Investment Research


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

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

Accuracy of content: 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 and have not sought for this information to be independently verified. Opinions contained in this report represent those of the research department of Edison at the time of publication. 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.

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

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

New Zealand

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

United Kingdom

This document is prepared and provided by Edison 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.

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.

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Frankfurt +49 (0)69 78 8076 960

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Germany

London +44 (0)20 3077 5700

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United Kingdom

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United States of America

Sydney +61 (0)2 8249 8342

Level 4, Office 1205

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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

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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