Last close As at 05/08/2026
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▲ −0.01 (−0.41%)
Market capitalisation
EUR247m
Research: Healthcare
Oryzon presented an updated set of data from the Phase IIa ALICE trial in acute myeloid leukaemia (AML) at this year’s virtual ASH conference (5–8 December). This is now the fourth update from the ALICE trial and the maturing data are consistent with the previously released positive 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, 11 (85%) 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 €560m or €10.6 per share (vs €9.9 per share previously).
Written by
Oryzon Genomics |
Response rates consistently high in ALICE trial |
R&D update |
Pharma & biotech |
11 December 2020 |
Share price performance
Business description
Next events
Analysts
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Oryzon presented an updated set of data from the Phase IIa ALICE trial in acute myeloid leukaemia (AML) at this year’s virtual ASH conference (5–8 December). This is now the fourth update from the ALICE trial and the maturing data are consistent with the previously released positive 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, 11 (85%) 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 €560m or €10.6 per share (vs €9.9 per share previously).
Year end |
Revenue (€m) |
PBT* |
EPS* |
DPS |
P/E |
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.
Consistent response rate
Besides dose-finding data and safety/tolerability evaluation (primary endpoints), initial efficacy was evaluated using the secondary endpoints: objective response rates (ORR), time to response and duration of response. These secondary endpoints were measured by bone marrow aspirate. Of the 18 enrolled patients, 13 had at least one aspirate and were evaluable. Of the 13 evaluable patients, 11 (85%) achieved OR (seven complete responses or complete responses with incomplete haematologic recovery and four partial responses). As the data have matured, Oryzon has reported durability results. Eight of the 13 evaluable patients (62%) had a durable response (over six months), while time to response and duration of response were 34 and 308 days, respectively (better durability means more likelihood there will be a clinical survival benefit; as the trial is still ongoing, data are yet to reach maturity).
Excellent comparative performance so far
These results are in line with the previously published updates from the ALICE trial (Exhibit 1). The OR rate is consistently 75–85% and is higher than the historical response rates with classic chemotherapy (25–32%). Moreover, such rates compare well with a novel combination chemotherapy that includes venetoclax, an 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, which will enrol up to 36 patients.
Valuation: €560m or €10.6 per share
Our valuation is slightly higher at €560m or €10.6 per share versus €527m or €9.9 per share due to rolling our model forward, which was partially offset by lower net cash. At end-Q320, Oryzon reported €44.6m in cash and €11.2m in total debt. We make no changes to our product assumptions for now.
Safety and tolerability
Overall, the authors of the ASH 2020 poster concluded that no new safety findings occurred since the last update and 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 were expected haematological AEs (neutropenia and thrombocytopenia). Only three non-haematological Grade 3–4 AEs were reported in two patients (asthenia and distortion of the sense of taste in one patient and weight reduction in another patient). Two serious AEs were considered to potentially relate to iadademstat, including one Grade 5 (fatal) intracranial haemorrhage, which was previously reported. 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, is that this fourth safety update shows the non-haematological safety profile of this combination treatment remains good.
Exhibit 1: Evolution of Phase IIa ALICE trial efficacy data
Trial/ regimen |
Phase IIa ALICE trial |
Venetoclax |
Azacitidine |
|||
Update/publication |
||||||
Enrolment |
17% (6/36) |
36% (13/36) |
50% (18/36) |
50% (18/36) |
- |
- |
Evaluable patients |
5 patients |
8 patients |
13 patients |
13 patients |
145 patients |
82 patients |
ORR |
80% (4/5) |
75% (6/8) |
77% (10/13) |
85% (11/13) |
68% (99/145) |
32% (26/82) |
Source: Edison Investment Research, Oryzon Genomics
Next steps
At the time of preparing the ASH 2020 poster, 18 patients had been enrolled in the trial, with a goal of recruiting up to 36 patients. Following interruptions in recruitment due to the COVID-19 pandemic, enrolment speed is now back up. Oryzon also stated that ‘considering the different mechanisms of action of proapoptotic BCL2 inhibitors and the pro-differentiating agent iadademstat, we believe that combination approaches with iadademstat might increase therapeutic options for patients in first line, as well as for refractory or intolerant patients who have received BCL2 inhibitors as first line’. We view this as an indication the company has gained the confidence to investigate iadademstat combination with chemotherapy across broader setting in AML, including first line and second line.
Valuation and financials
Our valuation is slightly higher at €560m or €10.6 per share versus €527m or €9.9 per share due to rolling our model forward, which was partially offset by lower net cash. Oryzon’s total operational spending for the first nine months (9m) of 2020 was €10.5m, flat compared to 9m19. Oryzon booked €7.3m as other income, which represents capitalised R&D costs (Oryzon follows local GAAP). The reported Q319 cash position was €44.6m (net cash €33.4m). Our model suggests the current cash position should be sufficient until 2023.
Exhibit 2: Oryzon NPV valuation
Product |
Indication |
Launch |
Peak sales |
Value |
Probability of success (%) |
rNPV |
NPV/share |
Iadademstat (ORY-1001) |
AML |
2023 |
927 |
313.0 |
15% |
62.0 |
1.2 |
Iadademstat (ORY-1001) |
SCLC |
2026 |
571 |
163.7 |
8% |
40.5 |
0.8 |
Vafidemstat (ORY-2001) |
AD |
2026 |
4,510 |
1,199.3 |
15% |
203.2 |
3.8 |
Vafidemstat (ORY-2001) |
MS |
2027 |
1,940 |
502.5 |
20% |
133.2 |
2.5 |
Vafidemstat (ORY-2001) |
BPD |
2027 |
1,340 |
335.7 |
20% |
87.9 |
1.7 |
Net cash (end-Q320) |
33.4 |
100% |
33.4 |
0.6 |
|||
Valuation |
|
|
2,547.5 |
560.2 |
10.6 |
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 |
|
2017 |
2018 |
2019 |
2020e |
2021e |
|
December |
Local GAAP |
Local GAAP |
Local GAAP |
Local GAAP |
Local GAAP |
||
PROFIT & LOSS |
|||||||
Revenue |
|
|
4,317 |
6,781 |
10,278 |
9,857 |
9,857 |
Cost of Sales |
0 |
0 |
0 |
0 |
0 |
||
Gross Profit |
4,317 |
6,781 |
10,278 |
9,857 |
9,857 |
||
Research and development |
(5,306) |
(7,412) |
(11,322) |
(11,060) |
(11,060) |
||
EBITDA |
|
|
(3,498) |
(2,766) |
(3,679) |
(4,091) |
(4,095) |
Operating Profit (before amort. and except.) |
|
|
(3,660) |
(2,905) |
(3,820) |
(4,225) |
(4,225) |
Intangible Amortisation |
(664) |
(7) |
(9) |
0 |
0 |
||
Exceptionals |
0 |
(4) |
(11) |
0 |
0 |
||
Other |
0 |
0 |
0 |
0 |
0 |
||
Operating Profit |
(4,324) |
(2,916) |
(3,839) |
(4,225) |
(4,225) |
||
Exceptionals |
0 |
0 |
0 |
0 |
0 |
||
Net Interest |
(928) |
(796) |
(737) |
(471) |
0 |
||
Profit Before Tax (norm) |
|
|
(4,588) |
(3,701) |
(4,557) |
(4,696) |
(4,225) |
Profit Before Tax (reported) |
|
|
(5,252) |
(3,712) |
(4,576) |
(4,696) |
(4,225) |
Tax |
55 |
2,535 |
892 |
1,713 |
1,302 |
||
Profit After Tax (norm) |
(4,533) |
(1,166) |
(3,666) |
(2,983) |
(2,922) |
||
Profit After Tax (reported) |
(5,197) |
(1,177) |
(3,685) |
(2,983) |
(2,922) |
||
Average Number of Shares Outstanding (m) |
31.7 |
34.6 |
41.6 |
45.8 |
45.8 |
||
EPS - normalised (€) |
|
|
(0.14) |
(0.03) |
(0.09) |
(0.07) |
(0.06) |
EPS - reported (€) |
|
|
(0.16) |
(0.03) |
(0.09) |
(0.07) |
(0.06) |
Dividend per share (€) |
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 |
|
|
24,914 |
31,786 |
42,357 |
52,196 |
62,039 |
Intangible Assets |
22,458 |
29,330 |
39,938 |
49,795 |
59,653 |
||
Tangible Assets |
638 |
665 |
631 |
613 |
598 |
||
Investments |
1,818 |
1,791 |
1,788 |
1,788 |
1,788 |
||
Current Assets |
|
|
36,130 |
35,664 |
37,738 |
43,012 |
29,445 |
Stocks |
7 |
135 |
289 |
289 |
289 |
||
Debtors |
857 |
971 |
2,071 |
1,521 |
1,796 |
||
Cash |
34,950 |
34,320 |
35,111 |
40,935 |
27,093 |
||
Other |
316 |
239 |
267 |
267 |
267 |
||
Current Liabilities |
|
|
(8,696) |
(10,441) |
(10,546) |
(9,642) |
(8,840) |
Creditors |
(1,343) |
(2,192) |
(4,000) |
(3,096) |
(2,293) |
||
Short term borrowings |
(7,354) |
(8,249) |
(6,547) |
(6,547) |
(6,547) |
||
Long Term Liabilities |
|
|
(17,915) |
(11,884) |
(8,420) |
(8,420) |
(8,420) |
Long term borrowings |
(16,041) |
(9,977) |
(6,699) |
(6,699) |
(6,699) |
||
Other long term liabilities |
(1,874) |
(1,907) |
(1,721) |
(1,721) |
(1,721) |
||
Net Assets |
|
|
34,432 |
45,125 |
61,129 |
77,146 |
74,223 |
CASH FLOW |
|||||||
Operating Cash Flow |
|
|
(4,281) |
(2,799) |
(3,610) |
(4,916) |
(5,172) |
Net Interest |
(426) |
2,133 |
(324) |
0 |
0 |
||
Tax |
0 |
0 |
0 |
1,713 |
1,302 |
||
Capex |
(105) |
(170) |
(115) |
(115) |
(115) |
||
Acquisitions/disposals |
0 |
0 |
0 |
0 |
0 |
||
Financing |
16,887 |
11,949 |
18,374 |
19,000 |
0 |
||
Other* |
653 |
(6,576) |
(9,916) |
(9,858) |
(9,590) |
||
Dividends |
0 |
0 |
0 |
0 |
0 |
||
Net Cash Flow |
12,728 |
4,538 |
4,409 |
5,824 |
(13,575) |
||
Opening net debt/(cash) |
|
|
1,172 |
(11,555) |
(16,093) |
(21,866) |
(27,689) |
HP finance leases initiated |
0 |
0 |
0 |
0 |
0 |
||
Other |
0 |
0 |
1,364 |
0 |
0 |
||
Closing net debt/(cash) |
|
|
(11,555) |
(16,093) |
(21,866) |
(27,689) |
(14,114) |
Source: Oryzon Genomics, Edison Investment Research. Note: Oryzon reports in Spanish GAAP. *Includes cash outflows related to development costs that were capitalised.
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Research: Healthcare
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