Third positive update from Phase II ALICE trial

Oryzon Genomics 15 June 2020 Update
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Oryzon Genomics

Third positive update from Phase II ALICE trial

R&D results

Pharma & biotech

15 June 2020

Price

€3.39

Market cap

€155m

Net cash (€m) at end Q120

18.4

Shares in issue

45.8m

Free float

70%

Code

ORY

Primary exchange

Madrid Stock Exchange

Secondary exchange

N/A

Share price performance

%

1m

3m

12m

Abs

(5.8)

108.0

(5.4)

Rel (local)

(12.7)

82.3

19.8

52-week high/low

€4.05

€1.63

Business description

Oryzon Genomics is a Spanish biotech focused on epigenetics. Iadademstat (Phase IIa) is being explored for acute leukaemias and SCLC; vafidemstat, its CNS product, is in Phase IIa trials in MS, AD and aggression. Newer asset ORY-3001 is being developed for certain orphan indications.

Next events

Potential start of Phase IIb PORTICO trial with vafidemstat in aggression in BPD. Timeline to be confirmed after the extent of COVID-19 pandemic is known

2020

Updated data from iadademstat Phase IIa CLEPSIDRA in SCLC

2020

Updated data from iadademstat Phase IIa ALICE in AML 2020

2020

Analyst

Jonas Peciulis

+44 (0)20 3077 5728

Oryzon Genomics is a research client of Edison Investment Research Limited

Last Friday, Oryzon presented an updated set of data from the Phase IIa ALICE trial in acute myeloid leukaemia (AML) at the virtual 25th Congress of the European Hematology Association (EHA-2020). This is now the third update from the ALICE trial and the maturing data are consistent with the previously released positive early efficacy results. The single-arm, open-label study enrolled newly diagnosed, elderly AML patients who were administered iadademstat in combination with standard of care chemotherapy drug azacitidine. Of the 13 evaluable patients, 10 (77%) achieved objective responses (OR). For comparison, OR rates are 25–32% in AML patients treated with azacitidine monotherapy. More data are due to follow. Our valuation is €496m or €10.8 per share.

Year end

Revenue (€m)

PBT*
(€m)

EPS*
(€)

DPS
(€)

P/E
(x)

Yield
(%)

12/18

6.8

(3.7)

(0.03)

0.0

N/A

N/A

12/19

10.3

(4.6)

(0.09)

0.0

N/A

N/A

12/20e

9.9

(4.7)

(0.07)

0.0

N/A

N/A

12/21e

9.9

(4.2)

(0.06)

0.0

N/A

N/A

Note: *Normalised, excluding amortisation of acquired intangibles and exceptional items.

Growing confidence in iada plus aza combo in AML

OR rates were assessed by bone marrow (BM) aspirate. Of the 18 enrolled patients, 13 had at least one BM aspirate and therefore were evaluable. Of the 13 evaluable patients, 10 (77%) achieved ORs: four complete responses (CRs), two CRs with incomplete haematologic recovery (CRi) and four partial responses (PR). These results are in line with the previously published updates from the ALICE trial. The OR rate is consistently 75–80% and is much higher than the historical response rates with classic chemotherapy (25–32%). Moreover, such rates compare well with a novel combination chemotherapy that includes venetoclax, a recently approved drug for front-line AML treatment (AbbVie/Genentech). Venetoclax plus azacitidine or decitabine achieved an OR rate of 67% in a late-stage trial and the consensus expects sales to reach $1.4bn in AML alone by 2026 (EvaluatePharma). More data will be released from the ALICE study.

No major disruption from COVID-19

As per its last update (17 April 2019) on the expected impact of the COVID-19 pandemic, Oryzon stated that despite all the precautionary measures none of the ongoing trials were cancelled and patient recruitment was not postponed. Hospital visits, when possible, were replaced by remote monitoring. Oryzon had planned to initiate a new Phase IIb trial in agitation-aggression in patients with borderline-personality disorder (PORTICO trial). This has now been postponed by ‘a few months’, which we believe is a manageable delay given the circumstances.

Valuation: €496m or €10.8 per share

Our valuation is slightly higher at €496m or €10.8 per share due to rolling our model forward, which is offset by lower net cash. As of end-Q120, Oryzon reported €29.3m in cash and €11.0m in total debt. We make no changes to our rNPV for the time being. A detailed review of all of the company’s ongoing programmes including upcoming catalysts can be found in our recent outlook report.

Phase IIa ALICE update

The single-arm, open-label study is enrolling newly diagnosed, elderly AML patients and investigates iadademstat in combination with standard-of-care chemotherapy drug azacitidine. At the time of writing the EHA-2020 poster, 18 patients have been enrolled.

Besides dose-finding data and safety/tolerability evaluation (primary endpoints), initial efficacy was evaluated using the secondary endpoints, OR, time to response (TTR) and duration of response (DOR). These secondary endpoints were measured by BM aspirate.

Of the 18 enrolled patients, 13 had at least one BM aspirate and therefore were evaluable (the last trial update released in December 2019 included data from eight evaluable patients). New data include:

10 of the 13 evaluable patients (77%) achieved ORs: four CRs, two CRis and four PRs.

TTR and DOR were 37 days and 20 weeks, respectively.

Exhibit 1: Patients enrolled in the Phase IIa ALICE trial

Source: Oryzon

Safety/tolerability

Overall, the authors of the EHA-2020 poster concluded that the combination of iadademstat and azacitidine shows a relatively good safety profile in elderly AML patients at the selected iadademstat’s dose level of 60µg/m2. Most patients experienced adverse events (AEs) that were considered related to the study drugs (azacitidine and/or iadademstat) and most of those AEs were neutropenia and thrombocytopenia. Only three non-haematological AEs (asthenia and distortion of the sense of taste in one patient and weight reduction in another patient) were observed. LSD1 inhibitor class drugs are known to have haematological side effects at higher doses. However, these are usually predictable and manageable. The key point, in our view, from this third safety data update is that the non-haematological safety profile of this combination treatment remains good.

Iadademstat/azacitidine combo efficacy results in perspective

OR rates in AML patients treated with azacitidine monotherapy are 25–32% depending on age (Maurillo et al, 2012). A recently published article (DiNardo et al, 2019) described a clinical trial (n=145) where AML patients received venetoclax plus azacitidine or decitabine (both chemical analogues of cytidine) and the OR rate was 67%. Venetoclax (Venclexta, AbbVie/Genentech) is a novel anticancer drug approved (accelerated approval) by the FDA for frontline treatment of AML in combination with azacitidine or decitabine or low-dose cytarabine.

In the first set of data from the ALICE trial published in June 2019, the OR rate was 80% in five evaluable patients. In the second data update released in December 2019, the OR rate was 75% in eight evaluable patients. The current update, now from 13 evaluable patients, shows an OR rate of 77%, so even though the patient number is still relatively small, the results clearly track the 75–80% range. This is much higher than the historical response rates with classic chemotherapy and compares well with venetoclax’s OR of 67%. Consensus expects venetoclax to reach $1.4bn in sales in AML alone by 2026 (EvaluatePharma).

Next steps

The second part of the ALICE study is still enrolling patients, so these results will be expanded in the coming months with additional patients and longer follow-up times. Oryzon also indicated that if these results are maintained, then ‘further trials with this combination therapy in a confirmatory study setting’ will be warranted.

Exhibit 2: Oryzon rNPV valuation

Product

Indication

Launch

Peak sales
(US$m)

Value
(€m)

Probability of success (%)

rNPV
(€m)

NPV/share
(€/share)

Iadademstat (ORY-1001)

AML

2023

927

311.3

15%

53.2

1.2

Iadademstat (ORY-1001)

SCLC

2026

571

160.2

8%

29.4

0.6

Vafidemstat (ORY-2001)

AD

2026

4,510

1,192.5

15%

192.0

4.2

Vafidemstat (ORY-2001)

MS

2027

1,940

523.7

20%

126.2

2.8

Vafidemstat (ORY-2001)

BPD

2027

1,290

322.4

20%

76.5

1.7

Net cash (end-2019)

18.4

100%

18.4

0.4

Valuation

 

 

2,528.5

495.7

10.8

Source: Edison Investment Research. Note: AML = acute myeloid leukaemia; SCLC = small cell lung cancer; AD = Alzheimer’s disease; MS = multiple sclerosis; BPD = borderline personality disorder.

Exhibit 3: Financial summary

€000s

 

2018

2019

2020e

2021e

Year end 31 December

Local GAAP

Local GAAP

Local GAAP

Local GAAP

PROFIT & LOSS

Revenue

 

 

6,781

10,278

9,857

9,857

Cost of Sales

0

0

0

0

Gross Profit

6,781

10,278

9,857

9,857

Research and development

(7,412)

(11,322)

(11,060)

(11,060)

EBITDA

 

 

(2,766)

(3,679)

(4,091)

(4,095)

Operating Profit (before amort. and except.)

(3,660)

(2,905)

(2,905)

(3,820)

Intangible Amortisation

(7)

(9)

0

0

Exceptionals

(4)

(11)

0

0

Other

0

0

0

0

Operating Profit

(2,916)

(3,839)

(4,225)

(4,225)

Exceptionals

0

0

0

0

Net Interest

(796)

(737)

(471)

0

Profit Before Tax (norm)

 

 

(3,701)

(4,557)

(4,696)

(4,225)

Profit Before Tax (reported)

 

 

(3,712)

(4,576)

(4,696)

(4,225)

Tax

2,535

892

1,713

1,302

Profit After Tax (norm)

(1,166)

(3,666)

(2,983)

(2,922)

Profit After Tax (reported)

(1,177)

(3,685)

(2,983)

(2,922)

Average Number of Shares Outstanding (m)

31.7

34.6

41.6

45.8

EPS - normalised (€)

 

 

(0.03)

(0.09)

(0.07)

(0.06)

EPS - reported (€)

 

 

(0.03)

(0.09)

(0.07)

(0.06)

Dividend per share (€)

0.0

0.0

0.0

0.0

Gross Margin (%)

100.0

100.0

100.0

100.0

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

 

 

31,786

42,357

52,196

62,039

Intangible Assets

29,330

39,938

49,795

59,653

Tangible Assets

665

631

613

598

Investments

1,791

1,788

1,788

1,788

Current Assets

 

 

35,664

37,738

24,012

10,445

Stocks

135

289

289

289

Debtors

971

2,071

1,521

1,796

Cash

34,320

35,111

21,935

8,093

Other

239

267

267

267

Current Liabilities

 

 

(10,441)

(10,546)

(9,642)

(8,840)

Creditors

(2,192)

(4,000)

(3,096)

(2,293)

Short term borrowings

(8,249)

(6,547)

(6,547)

(6,547)

Long Term Liabilities

 

 

(11,884)

(8,420)

(8,420)

(8,420)

Long term borrowings

(9,977)

(6,699)

(6,699)

(6,699)

Other long term liabilities

(1,907)

(1,721)

(1,721)

(1,721)

Net Assets

 

 

45,125

61,129

58,146

55,223

CASH FLOW

Operating Cash Flow

 

 

(2,799)

(3,610)

(4,916)

(5,172)

Net Interest

2,133

(324)

0

0

Tax

0

0

1,713

1,302

Capex

(170)

(115)

(115)

(115)

Acquisitions/disposals

0

0

0

0

Financing

11,949

18,374

0

0

Other*

(6,576)

(9,916)

(9,858)

(9,590)

Dividends

0

0

0

0

Net Cash Flow

4,538

4,409

(13,176)

(13,575)

Opening net debt/(cash)

 

 

(11,555)

(16,093)

(21,866)

(8,689)

HP finance leases initiated

0

0

0

0

Other

0

1,364

0

0

Closing net debt/(cash)

 

 

(16,093)

(21,866)

(8,689)

4,886

Source: Edison Investment Research, Oryzon Genomics accounts. Note: Oryzon reports in Spanish GAAP. *Includes cash outflows related to development costs that were capitalised.


General disclaimer and copyright

This report has been commissioned by Oryzon Genomics and prepared and issued by Edison, in consideration of a fee payable by Oryzon Genomics. 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.

Exclusion of Liability: To the fullest extent allowed by law, Edison shall not be liable for any direct, indirect or consequential losses, loss of profits, damages, costs or expenses incurred or suffered by you arising out or in connection with the access to, use of or reliance on any information contained on this note.

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

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

Copyright: Copyright 2020 Edison Investment Research Limited (Edison).

Australia

Edison Investment Research Pty Ltd (Edison AU) is the Australian subsidiary of Edison. Edison AU is a Corporate Authorised Representative (1252501) of Crown Wealth Group Pty Ltd who holds an Australian Financial Services Licence (Number: 494274). 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

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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.

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.

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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

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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

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United States of America

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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

General disclaimer and copyright

This report has been commissioned by Oryzon Genomics and prepared and issued by Edison, in consideration of a fee payable by Oryzon Genomics. 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.

Exclusion of Liability: To the fullest extent allowed by law, Edison shall not be liable for any direct, indirect or consequential losses, loss of profits, damages, costs or expenses incurred or suffered by you arising out or in connection with the access to, use of or reliance on any information contained on this note.

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

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

Copyright: Copyright 2020 Edison Investment Research Limited (Edison).

Australia

Edison Investment Research Pty Ltd (Edison AU) is the Australian subsidiary of Edison. Edison AU is a Corporate Authorised Representative (1252501) of Crown Wealth Group Pty Ltd who holds an Australian Financial Services Licence (Number: 494274). 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.

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

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

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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