Last close As at 05/08/2026
EUR3.22
▲ −0.05 (−1.41%)
Market capitalisation
EUR77m
Research: Healthcare
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.
Written by
OSE Immunotherapeutics |
Progress with key R&D assets |
Company update |
Pharma & biotech |
13 March 2020 |
Share price performance
Business description
Next events
Analyst
OSE Immunotherapeutics is a research client of Edison Investment Research Limited |
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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* |
EPS* |
DPS |
P/E |
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).
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Exhibit 1: Overall survival and immune response to Tedopi epitopes |
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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.
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Exhibit 2: CD47/SIRP-α pathway |
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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.
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Exhibit 3: OSE’s R&D pipeline |
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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 |
Unrisked NPV (€m) |
Unrisked NPV/share (€) |
Probability |
rNPV |
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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