OSE Immunotherapeutics — Progress with key R&D assets

OSE Immunotherapeutics (PAR: OSE)

Last close As at 23/04/2024

EUR5.97

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EUR118m

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Research: Healthcare

OSE Immunotherapeutics — Progress with key R&D assets

OSE has a well-balanced R&D pipeline in terms of asset stage and technology. In the near term, much of the focus is on Tedopi, an off-the-shelf cancer vaccine, as it is the most advanced asset in development, and the Phase III Atalante 1 trial in NSCLC, which is ongoing, with a pre-defined step 1 patient survival assessment expected by end-Q120. Other recent news includes successful completion of the Phase I study with OSE-127 (anti-IL-7R) and the Tedopi out-licensing deal in South Korea. Our valuation is higher at €227m or €15.2/share (previously €198m) due to the increase in OSE-127’s success probability after the positive Phase I study.

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Healthcare

OSE Immunotherapeutics

Progress with key R&D assets

Company update

Pharma & biotech

13 March 2020

Price

€3.26

Market cap

€49m

Gross cash (€m) at end-H119 (government debt not included)

26.5

Shares in issue

15.0m

Free float

25%

Code

OSE

Primary exchange

Euronext Paris

Secondary exchange

N/A

Share price performance

%

1m

3m

12m

Abs

(18.7)

(9.4)

(20.3)

Rel (local)

22.4

31.0

4.1

52-week high/low

€4.30

€3.26

Business description

OSE Immunotherapeutics is an immunotherapy company based in Nantes and Paris, France, and listed on the Euronext Paris exchange. OSE is developing immunotherapies for the treatment of solid tumours and autoimmune diseases and has established several partnerships with large pharma companies.

Next events

Phase III Atalante 1 step 1 assessment

Q120

FY19 results

26 March 2020

Initiation of Phase II trials with OSE-127

2020

Update on BiCKI platform

2020

Analyst

Jonas Peciulis

+44 (0)20 3077 5728

OSE Immunotherapeutics is a research client of Edison Investment Research Limited

OSE has a well-balanced R&D pipeline in terms of asset stage and technology. In the near term, much of the focus is on Tedopi, an off-the-shelf cancer vaccine, as it is the most advanced asset in development, and the Phase III Atalante 1 trial in NSCLC, which is ongoing, with a pre-defined step 1 patient survival assessment expected by end-Q120. Other recent news includes successful completion of the Phase I study with OSE-127 (anti-IL-7R) and the Tedopi out-licensing deal in South Korea. Our valuation is higher at €227m or €15.2/share (previously €198m) due to the increase in OSE-127’s success probability after the positive Phase I study.

Year end

Revenue (€m)

PBT*
(€m)

EPS*
(€)

DPS
(€)

P/E
(x)

Yield
(%)

12/17

6.7

(12.6)

(0.72)

0.0

N/A

N/A

12/18

24.5

4.8

0.38

0.0

N/M

N/A

12/19e

16.6

(6.1)

(0.41)

0.0

N/A

N/A

12/20e

0.0

(22.8)

(1.53)

0.0

N/A

N/A

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

Phase III Atalante 1 trial step 1 check in Q120

This is a Phase III trial with Tedopi as second- or third-line treatment vs standard of care (docetaxel or pemetrexed) in HLA-A2 positive patients with locally advanced (stage IIIB), or metastatic (stage IV) NSCLC. Post-checkpoint inhibitor treatment failure patients represent an area where no novel treatment has been approved yet. Predefined step 1 assessment is expected by end-Q120. If 30 out the first 84 patients reach an OS of 12 months, then the study will continue as planned. In total, 350 patients are expected to be recruited. Full results should be available in 2021.

New analysis from Tedopi Phase II trial

In November 2019, OSE presented new analysis from the completed Phase II trial at the 2019 Society for Immunotherapy of Cancer (SITC) Annual Meeting in National Harbor, Maryland, US. The data clearly demonstrated that those patients who have developed an immune response to Tedopi epitopes had better survival, which supports Tedopi’s mechanism of action.

Positive results from Phase I study with OSE-127

In December 2019, OSE announced the successfully completion of its Phase I study with OSE-127 in ulcerative colitis (UC). The results showed a good safety and tolerability profile, while accumulated PK/PD data allowed the recommended dose to be selected for the Phase II trials. OSE is developing OSE-127 in partnership with Servier, which has a two-step option to in-license the drug candidate after completion of the Phase II trials. OSE confirmed its plans to initiate two studies in UC and Sjögren’s syndrome. Both trials should begin in 2020.

Valuation: €227m or €15.2/share

We have raised our valuation of OSE to €227m or €15.2/share from €198m or €13.2/share previously, mainly due to the increased success probability for OSE-127 and rolling the model forward. We make no other changes to our assumptions, described in detail in our initiation report. FY19 results are due on 26 March 2020.

New neoepitope response and survival analysis from Tedopi Phase II trial

As a reminder, this was an open-label, single-arm trial that enrolled 64 HLA-A2 positive patients, who received Tedopi for two years. We described the results of the trial (primary and secondary endpoints) in detail in our initiation report. In the newly presented analysis at the SITC conference in November 2019, OSE assessed whether the overall survival of patients could be predicted by the number and type of epitopes to which the patients developed an immune response.

In total, 33 out of 64 treated patients were assessed for an epitope-specific immune response (cytotoxic response and helper T-lymphocyte responses). Tedopi comprises 10 neoepitopes. Of those 33 patients, 11 had all 10 epitopes evaluated, while all 33 patients had six epitopes evaluated (2 CEA, 1 HER-2, MAGE-2, MAGE-3, PADRE). Results showed that:

T-cell responses to the epitopes were demonstrated in the majority of patients, where 91% had a response to at least one epitope; eight epitopes were highly immunogenic (from 55% to 91%), while HER-2 wild type and one p53 analogue showed a lower response (36% and 9%, respectively).

The key finding was that survival was significantly improved in those patients who have developed an immune response to Tedopi epitopes. For example, patients who developed immune responses to 3-6 epitopes (n=23) had a median overall survival of 38 months compared to 15 months in patients (n=10) with responses to 0-2 epitopes (p=0.04) (Exhibit 1). Similarly, patients who developed responses to 2-6 epitopes survived significantly longer than those who developed response to 0-1 epitopes. This was also true in patients who had responses to 1-6 epitopes compared to those who had no response.

These results support Tedopi’s expected mechanism of action – priming a tumour-specific immune response. The goal of the ongoing Phase III Atalante 1 trial is to show that the vaccine can add clinical benefit to standard of care in HLA-A2-positive advanced NSCLC (c 45% of the total population).

Exhibit 1: Overall survival and immune response to Tedopi epitopes

Source: OSE, SITC 2019

Tedopi out-licensed in South Korea

In November 2019, OSE announced that it had out-licensed the rights to Tedopi in South Korea to Chong Kun Dang (CKD) Pharmaceutical Corporation. The deal terms include upfront and short-term milestone payments of €1.2m, total milestone payments of €4.3m and royalties in the high twenties.

Since OSE has only out-licensed Tedopi rights in South Korea, the financial benefit was understandably limited. In our view, the more important aspect of this deal is external validation of OSE’s technology, as presumably CKD carried out extensive due diligence. Although no details of the development plans have been released yet, CKD is a diversified pharmaceutical company in South Korea with a broad R&D pipeline, and therefore an appropriate partner for OSE in this market.

Positive results from Phase I study with anti-IL-7R OSE-127

In December 2019, OSE announced that it had successfully completed the Phase I study with OSE-127. This was a first-in-human, dose escalation (single- and multiple-ascending), randomised, double-blind, placebo-controlled study that tested OSE-127 in 63 healthy volunteers. The results showed a good safety and tolerability profile, while accumulated PK/PD data allowed the recommended dose to be selected for Phase II trials.

OSE is developing OSE-127 in partnership with Servier, which has a two-step option to in-license it after completion of the Phase II trials. The total deal value was €272m, including a €10.3m upfront payment (received in 2016), a two-step €30m option exercise fee, development and commercial milestones, plus double-digit royalties on sales. At the start of the Phase I study, OSE received €10m of the €30m, so €20m are still due if Servier decides to exercise the option.

OSE-127 is a humanised monoclonal antibody against IL-7Rα, specifically CD127, a cytokine that controls the proliferation, apoptosis and activation of CD4 and CD8 T-cells in humans. As a next step, OSE confirmed its previous plans to initiate two studies in ulcerative colitis (UC) and Sjögren’s syndrome. Both trials are expected to begin in 2020. As per the agreement with Servier, the UC study will be sponsored by OSE (co-financed by Bpifrance) and Servier has the option to in-license development afterwards. In parallel, Servier will run the Sjögren’s syndrome study on its own.

Phase I study with BI 765063 (OSE-172) ongoing

BI 765063 (OSE-172) is a SIRP-α antagonist for solid tumours. The CD47/SIRP-α space continues to attract significant interest from large pharma and biotech companies. We described the evolving landscape in our initiation report, where we identified a US biotech, Forty Seven, as the leader in the anti-CD47 antibody space with its main asset Hu5F9-G4 in several Phase I/II trials. Founded in 2015, Forty Seven was acquired by Gilead Sciences in March 2020 for $4.9bn (a 96% premium). CD47, which is present in tumour cells, is a more widely studied target, with several companies running early to mid-stage clinical trials. In the SIRP-α inhibitor space, however, OSE’s BI 765063 (OSE-172) is one of the most advanced programmes to our knowledge.

BI 765063 is expected to work in a similar way to T-cell immune checkpoint inhibitors in the tumour microenvironment, but instead of T-cells, it inhibits the checkpoints between tumour cells and myeloid cells: myeloid-derived suppressor cells (MDSCs) and tumour-associated macrophages (TAMs). It binds to signal regulatory peptide alpha (SIRPα) on myeloid cells, which inhibits the SIRPα/CD47 interaction (CD47 on the surface of cancer cells). CD47 acts as a ‘don't eat me’ signal to macrophages of the immune system, so when blocked this increases the likelihood that the myeloid cell recognises the cancer cell as foreign, then attacks and digests the cancer cell. Phagocytosis leads to presentation of cancer antigens on the surface, which stimulates the immune system.

Exhibit 2: CD47/SIRP-α pathway

Source: OSE

The currently ongoing Phase I study with BI 765063 is run by OSE but funded by Boehringer Ingelheim (BI). According to the terms of the licensing deal with BI, OSE is eligible to receive up to €1.1bn in milestones plus royalties if certain conditions are met. OSE initiated the Phase I study in June 2019, but BI will take over development after Phase I. Phase I is an open-label, dose-finding study (n=116) of BI 765063 as single agent and in combination with BI 754091 (anti-PD-1) to characterise safety, PK/PD and preliminary efficacy in patients with advanced solid tumours.

Exhibit 3: OSE’s R&D pipeline

Source: OSE

Valuation

We have raised our valuation of OSE to €227m or €15.2/share from €198m or €13.2/share previously, mainly due to rolling the model forward and increasing the probability of success for OSE-127 in UC to 15% from 10%. We make no other changes to our assumptions, described in detail in our initiation report. OSE will report FY19 financial results on 26 March 2020.

We include Tedopi for NSCLC, FR104, OSE-127 and OSE-172 in our valuation. Although GERCOR has initiated a Phase II study with Tedopi in pancreatic cancer, we do not yet include this indication in our valuation because its commercial strategy has not been confirmed – OSE will evaluate this based on the Phase II results. Nor do we include the new bi-specific platform in the valuation because it is still at the preclinical stage.

Exhibit 4: Sum-of-the-parts OSE valuation

Product

Launch

Peak sales
($m)

Unrisked NPV (€m)

Unrisked NPV/share (€)

Probability
(%)

rNPV
(€m)

rNPV/share
(€)

Tedopi – NSCLC

2023

657

291.9

19.5

25%

69.4

4.6

OSE-127 - ulcerative colitis

2027

843

181.6

12.1

15%

34.7

2.3

OSE-172 - multiple cancer indications (TNBC)

2027

1,801

273.1

18.2

10%

38.7

2.6

FR104 - rheumatoid arthritis

2026

1,056

242.9

16.2

15%

58.5

3.9

FY19e cash*

25.5

1.7

100%

25.5

1.7

Valuation

1,015.0

67.8

226.8

15.2

Source: Edison Investment Research. Note: WACC = 12.5% for product valuations. Note: *OSE’s debt, not shown above, consists of government loans, which are typically repayable on commercial success only.

Exhibit 5: Financial summary

€'000s

2017

2018

2019e

2020e

December

IFRS

IFRS

IFRS

IFRS

PROFIT & LOSS

Revenue

 

 

6,682

24,456

16,579

0

Cost of Sales

0

0

0

0

Gross Profit

6,682

24,456

16,579

0

Research and development

(14,641)

(15,057)

(17,000)

(17,000)

EBITDA

 

 

(12,502)

4,963

(5,988)

(22,746)

Operating Profit (before amort. and except.)

 

 

(12,625)

4,847

(6,079)

(22,827)

Intangible Amortisation

0

0

0

0

Exceptionals

0

0

0

0

Other

0

0

0

0

Operating Profit

(12,625)

4,847

(6,079)

(22,827)

Net Interest

0

0

(1)

(6)

Profit Before Tax (norm)

 

 

(12,625)

4,847

(6,080)

(22,833)

Profit Before Tax (reported)

 

 

(12,625)

4,847

(6,080)

(22,833)

Tax

2,238

783

0

0

Profit After Tax (norm)

(10,387)

5,630

(6,080)

(22,833)

Profit After Tax (reported)

(10,387)

5,630

(6,080)

(22,833)

Average Number of Shares Outstanding (m)

14.4

14.6

14.8

15.0

EPS - normalised (€)

 

 

(0.72)

0.38

(0.41)

(1.53)

EPS - normalised fully diluted (€)

 

 

(0.72)

0.36

(0.41)

(1.53)

EPS - reported (€)

 

 

(0.72)

0.38

(0.41)

(1.53)

Dividend per share (€)

0.0

0.0

0.0

0.0

Gross Margin (%)

100.0

100.0

100.0

N/A

EBITDA Margin (%)

N/A

20.3

N/A

N/A

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

N/A

19.8

N/A

N/A

BALANCE SHEET

Fixed Assets

 

 

53,367

53,879

55,617

55,535

Intangible Assets

52,600

52,600

52,600

52,600

Tangible Assets

429

904

814

732

Investments

338

375

2,203

2,203

Current Assets

 

 

12,655

14,687

26,709

4,802

Stocks

0

0

0

0

Debtors

127

2,253

1,178

1,178

Cash

9,646

9,573

22,670

3,624

Other

2,882

2,861

2,861

0

Current Liabilities

 

 

(14,497)

(9,075)

(20,909)

(20,909)

Creditors

(13,908)

(8,447)

(20,253)

(20,253)

Short term borrowings

(589)

(628)

(656)

(656)

Long Term Liabilities

 

 

(7,409)

(6,075)

(16,324)

(16,324)

Long term borrowings

(4,296)

(3,832)

(9,293)

(9,293)

Other long term liabilities

(3,113)

(2,243)

(7,031)

(7,031)

Net Assets

 

 

44,116

53,416

45,093

23,105

CASH FLOW

Operating Cash Flow

 

 

(7,995)

1,860

7,611

(21,901)

Net Interest

0

0

(1)

(6)

Tax

0

(783)

0

0

Capex

(353)

(593)

0

0

Acquisitions/disposals

0

0

0

0

Financing

(50)

(37)

0

0

Other

58

(95)

0

2,861

Dividends

0

0

0

0

Net Cash Flow

(8,340)

352

7,609

(19,046)

Opening net debt/(cash)

 

 

(13,101)

(4,761)

(5,113)

(12,721)

HP finance leases initiated

0

0

0

0

Other

0

(0)

0

0

Closing net debt/(cash)

 

 

(4,761)

(5,113)

(12,722)

6,325

Source: Company data, Edison Investment Research


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This report has been commissioned by OSE Immunotherapeutics and prepared and issued by Edison, in consideration of a fee payable by OSE Immunotherapeutics. 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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General disclaimer and copyright

This report has been commissioned by OSE Immunotherapeutics and prepared and issued by Edison, in consideration of a fee payable by OSE Immunotherapeutics. 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). All rights reserved FTSE International Limited (“FTSE”) © FTSE 2020. “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.

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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 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.

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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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Euromoney Institutional Investor — COVID-19 potential impact

Euromoney has outlined the impact to date of Coronavirus COVID-19 on its events business and listed its short-term schedule that may be subject to postponement or cancellation. June is a large month for the group’s events and decisions are yet to be taken about these. Our revised model takes the view that these events do not proceed, but that those scheduled for September do. We have assumed a small residual impact in FY21 as the programme is reconfigured. This group’s share price continues to sit at a marked discount to peers, reflecting the uncertainty associated with the strategic review, despite the intrinsically strong business model.

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