Hybrigenics has published data from a Phase II study in chronic myeloid leukaemia (CML). After one year of treatment, 40% of patients showed improvements beyond a major molecular response (MMR) and 20% achieved a deep molecular response (DMR), consistent with a functional cure. The ongoing Phase II trial in acute myeloid leukaemia (AML) will complete enrolment before end 2018, with data readout in 2019. Hybrigenics has completed its refocusing on R&D with the sale of the genomics division, Helixio. The internal R&D programme on ubiquitin-specific proteases (USP) inhibition continues. Hybrigenics also has an R&D partnership with Servier focused on oncology worth up to €12m. Cash at end 2017 was €7m. Our valuation is €129.5m or €2.77/share.
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Hybrigenics |
Leukaemia pipeline advances with new data |
FY17 update |
Pharma & biotech |
24 May 2018 |
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Hybrigenics is a research client of Edison Investment Research Limited |
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Hybrigenics has published data from a Phase II study in chronic myeloid leukaemia (CML). After one year of treatment, 40% of patients showed improvements beyond a major molecular response (MMR) and 20% achieved a deep molecular response (DMR), consistent with a functional cure. The ongoing Phase II trial in acute myeloid leukaemia (AML) will complete enrolment before end 2018, with data readout in 2019. Hybrigenics has completed its refocusing on R&D with the sale of the genomics division, Helixio. The internal R&D programme on ubiquitin-specific proteases (USP) inhibition continues. Hybrigenics also has an R&D partnership with Servier focused on oncology worth up to €12m. Cash at end 2017 was €7m. Our valuation is €129.5m or €2.77/share.
Year end |
Revenue (€m) |
PBT* |
EPS* |
DPS |
P/E |
Yield |
12/16* |
2.6 |
(4.0) |
(11.2) |
0.0 |
N/A |
N/A |
12/17 |
1.9 |
(7.3) |
(17.7) |
0.0 |
N/A |
N/A |
12/18e |
3.6 |
(4.1) |
(8.7) |
0.0 |
N/A |
N/A |
12/19e |
2.2 |
(4.0) |
(7.6) |
0.0 |
N/A |
N/A |
Note: *PBT and EPS are normalised, excluding intangible amortisation and exceptionals. *12/16 corresponds to retained activities.
CML trial reads out; AML data on track for 2019
In CML a DMR may be considered a functional cure and stopping treatment (even temporarily) can be an option. The Phase II study in CML showed that 40% (8/20) of patients had a decrease of BCL-ABL beyond 3 log, which is an MMR. A decrease of more than 4.5 log was achieved by 20% (4/20) of patients. These data are lower than previous interim data released in February 2017 where MMR was 43% and DMR was 33%. Separately, the Phase II study in AML in combination with decitabine has enrolled 87 of the planned 110 patients. The company expects to complete enrolment by this year’s end and report results in 2019. To maximise the cash runway, Hybrigenics will assess the next studies in CML, chronic lymphocytic leukaemia (CLL) and prostate cancer once the AML data are announced.
R&D refocus completed; USP research continues
Hybrigenics has sold its genomics division, Helixio (financial terms not disclosed), which completes the company’s refocusing on R&D initiated last year with the sale of its controlling stake in Hybrigenics Services, its subsidiary dedicated to proteomics. Hybrigenics is now a pure R&D company focused on inecalcitol and drug discovery of inhibitors of USPs. The company’s broad spectrum USP inhibitor, HBX 47,939, has been shown to inhibit viral replication and decrease the production of new virions in in vitro experiments. Hybrigenics continues its internal R&D programme focused on USP inhibitors, particularly of USP7, USP8 and USP10, for oncology. Hybrigenics also has an R&D collaboration with Servier on USP inhibitors in oncology worth up to €12m in potential payments until registration.
Valuation: rNPV of €129.5m or €2.77/share
Our valuation is now €129.5m or €2.77/share (from €121m or €2.6/share). We have pushed back the launch of inecalcitol in CML by one year. We have rolled the model forward in time and updated the FY17 net cash position of €6.9m.
Advancing leukaemia programmes; AML data in 2019
Data from the CML study showed that after one year, eight out of 20 patients (40%) achieved a reduction of more than 3 log, which is considered a MMR, and four out of 20 patients (20%) achieved a DMR, which is a reduction of 4.5 log or more, meeting the primary endpoint of the trial. In this open-label Phase II study, inecalcitol was administered in combination with oral imatinib in CML patients with incomplete molecular response after at least two years on imatinib. Molecular response is a measure of efficacy used in CML that determines the expression of BCL-ACR by polymerase chain reaction in circulating blood cells. The trial was conducted in France and enrolled 22 patients (from the previous target of 42) of which 20 completed one year of treatment.
Achieving lasting DMRs could reduce treatment costs by taking the patient off treatment earlier. This would represent an innovative approach to improve patients’ quality of life and reduce costs from current expensive treatments. For instance, Gleevec’s list price is $120k per year, per patient in the US; Sprycel and Tasigna cost approximately the same, while in Europe most tyrosine-kinase inhibitors cost around $30k per year per patient. Inecalcitol could fit in this strategy and become an adjunct to other therapies, rather than directly competing with them. We believe the Phase II initial data show the potential impact of inecalcitol on the CML treatment paradigm, due to its benign safety profile and potential to further improve molecular responses leading to discontinuation of treatment and functional cures. This potential, however, will have to be confirmed in randomised, controlled late-stage clinical trials to fully assess the benefit of adding inecalcitol to current treatments in patients with CML.
We note this was a small trial with the inherent biases associated with open-label studies. The lack of a comparator arm further complicates the interpretation of the data. Historic data show 1% DMR at one year in the imatinib arm in the ENESTnd study and 3% in the DASISION study.
We estimate c 14,250 new CML patients per year in the EU and the US (sources: US National Cancer Institute’s Surveillance, Epidemiology and End Results programme and the European Treatment and Outcomes Study for CML). We maintain our forecast of EU/US peak sales for inecalcitol of $257m in CML. Hybrigenics plans to apply for orphan drug status in the EU and US based on these data.
Due to the need to focus resources, Hybrigenics will wait for the outcome of the AML study to decide on the next steps for the CML programme, as well as CLL and prostate cancer. Hybrigenics expects to publish results from the Phase II study with inecalcitol in patients with AML in 2019. Recruitment is well on track to complete its target of 110 patients by this year’s end; 87 patients have been enrolled so far, mostly in the US and France. Other European countries such as Spain and Belgium are recruiting patients. This is a double-blind, placebo-controlled trial in patients over 65 years old and unfit for chemotherapy. Daily doses of oral inecalcitol (4mg) or placebo will be administered to patients who can only receive monthly cycles of decitabine infusions. The primary endpoint is overall survival. Inecalcitol has orphan drug status for AML in Europe and the US.
We estimate c 40,000 new AML patients in the EU and US and forecast inecalcitol peak sales of $119m in this indication.
Financials: FY17 results
Hybrigenics’s full-year 2017 results reflect the R&D reorganisation of the company, which involved the sale of its stakes in Hybrigenics Services, its proteomics subsidiary; and of Helixio, its genomics division. Hybrigenics reports the results of its retained activities, which comprise the development of inecalcitol and research on ubiquitin-specific proteases.
FY17 revenues were c €1.9m, which comprises subleases, services to sub-leasers and 2017 research tax credit. This is a 73% increase compared to other operating revenues of €1.1m in 2016. Total revenues were down 27% from €2.6m in 2016 to €1.9m in 2017 as there were no milestone payments from the ongoing collaboration with Servier. We forecast lower revenues of €3.6m in 2018 vs €5.5m previously due to discontinued revenues from services and less tax credit. We project a potential milestone payment from Servier of €1.5m in 2018.
FY17 operating costs were €9.3m vs €6.6m in FY16. We forecast that there will be a decrease in FY18 operating expenses to €7.7m, down from our previous forecast of €10m due to decreased R&D expenditure as the CML trial was completed before we expected (estimated H218).
Hybrigenics’s net cash position was €6.9m as at end-2017. We estimate this should be sufficient to fund operations into the second half of 2019. However, we expect the group to move into a cash shortfall during 2019, which we have assumed will require new funds of €5m in the form of long-term debt, for modelling purposes.
Valuation: rNPV of €129.5m
Our updated valuation is €129.5m or €2.77/share (previously €121m or €2.6/share). As development in CML is paused until the release of the AML data next year, we have pushed back the launch date by one year, from 2020 to 2021 in the EU and US. This is offset by rolling the model forward in time.
We maintain the probability of success in CML at 40% and 30% in AML. We include inecalcitol in CLL in our valuation with a probability of success of 20%; we will update this next year when the company announces its plans after the release of data from the AML trial.
We include our forecast of the milestone payments from the collaboration with Servier and our forecast of revenues associated with subleases, tax credits and services. We exclude preclinical projects and prostate cancer from our valuation.
Exhibit 1: Financial summary
€'000s |
2016* |
2017 |
2018e |
2019e |
||
Year end 31 December |
IFRS |
IFRS |
IFRS |
IFRS |
||
PROFIT & LOSS |
||||||
Revenue |
|
|
2,581 |
1,880 |
3,568 |
2,171 |
Cost of sales |
22 |
0 |
0 |
0 |
||
Gross profit |
2,603 |
1,880 |
3,568 |
2,171 |
||
EBITDA |
|
|
(3,493) |
(6,781) |
(3,528) |
(3,318) |
Intangible amortisation |
(119) |
(280) |
(280) |
(280) |
||
Share-based payments |
(166) |
(68) |
(125) |
(150) |
||
Operating profit (before amort. and except.) |
|
(4,023) |
(7,377) |
(4,181) |
(3,996) |
|
Exceptionals |
0 |
0 |
0 |
0 |
||
Operating profit |
(4,023) |
(7,377) |
(4,181) |
(3,996) |
||
Net interest and other financial items |
31 |
83 |
121 |
12 |
||
Profit before tax (norm) |
|
|
(3,992) |
(7,294) |
(4,060) |
(3,983) |
Profit before tax (reported) |
|
|
(3,993) |
(7,293) |
(4,060) |
(3,983) |
Tax |
0 |
0 |
0 |
0 |
||
Profit after tax (norm) |
(3,992) |
(7,293) |
(4,059) |
(3,981) |
||
Profit after tax (reported) |
(3,992) |
(7,293) |
(4,059) |
(3,981) |
||
Discontinued operations |
(1,259) |
(664) |
0 |
0 |
||
Net income (norm) |
(3,992) |
(7,293) |
(4,059) |
(3,980) |
||
Net income (reported) |
(5,252) |
(7,957) |
(4,060) |
(3,983) |
||
Average number of shares outstanding (m) |
35.8 |
41.3 |
46.8 |
52.2 |
||
EPS - normalised (c) |
|
|
(11.2) |
(17.7) |
(8.7) |
(7.6) |
EPS - FRS 3 (c) |
|
|
(14.7) |
(19.3) |
(8.7) |
(7.6) |
Dividend per share (c) |
0.0 |
0.0 |
0.0 |
0.0 |
||
Gross margin (%) |
101% |
100% |
100% |
100% |
||
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 |
|
|
1,133 |
1,303 |
975 |
646 |
Intangible assets |
524 |
518 |
238 |
-42 |
||
Tangible assets |
326 |
238 |
190 |
141 |
||
Investments |
283 |
547 |
547 |
547 |
||
Current assets |
|
|
15,048 |
12,570 |
8,280 |
9,775 |
Stocks |
55 |
0 |
0 |
0 |
||
Debtors |
546 |
1,276 |
2,422 |
1,475 |
||
Cash |
8,489 |
7,015 |
1,579 |
4,020 |
||
Other |
3,833 |
4,279 |
4,279 |
4,279 |
||
Assets held for sale |
2,125 |
0 |
0 |
0 |
||
Current liabilities |
|
|
(4,955) |
(4,367) |
(3,686) |
(3,686) |
Creditors |
(1,565) |
(2,409) |
(1,726) |
(1,725) |
||
Short-term borrowings |
(91) |
(97) |
(97) |
(97) |
||
Other |
(1,145) |
(1,861) |
(1,863) |
(1,864) |
||
Liabilities associated with assets held for sale |
(2,154) |
0 |
0 |
0 |
||
Non-current liabilities |
|
|
(346) |
(306) |
(306) |
(306) |
Long-term borrowings |
0 |
0 |
0 |
0 |
||
Other |
(346) |
(306) |
(306) |
(306) |
||
Net assets |
|
|
10,881 |
9,200 |
5,263 |
6,428 |
CASH FLOW |
||||||
Operating cash flow |
|
|
(2,494) |
(7,573) |
(5,357) |
(2,372) |
Net interest |
6 |
(24) |
121 |
12 |
||
Tax |
0 |
0 |
0 |
0 |
||
Capex |
(199) |
(136) |
(200) |
(199) |
||
Payment of deferred consideration |
0 |
0 |
0 |
0 |
||
Capitalisation of development costs |
0 |
0 |
0 |
0 |
||
Expenditure on intangibles |
0 |
0 |
0 |
0 |
||
Acquisitions/disposals |
0 |
0 |
0 |
0 |
||
Financing |
(228) |
6,257 |
0 |
5,000 |
||
Dividends |
0 |
0 |
0 |
0 |
||
Net cash flow |
(2,915) |
(1,476) |
(5,436) |
2,441 |
||
Opening net debt/(cash) |
|
|
(11,314) |
(8,398) |
(6,918) |
(1,482) |
HP finance leases initiated |
0 |
0 |
0 |
0 |
||
Other |
(1) |
(4) |
0 |
0 |
||
Closing net debt/(cash) |
|
|
(8,398) |
(6,918) |
(1,482) |
(3,923) |
Source: Edison Investment Research, company accounts. Reinstated to reflect discontinuation of Helixio activities.
|
|
Research: Healthcare
With its Q118 results, RedHill reported GI product revenues growing by 22% q-o-q to $2.4m in Q118. It also provided updates on its Phase III programmes. The last patient has been assessed against the primary endpoint in the RHB-104 first Phase III trial in Crohn’s disease (CD), and top-line data are expected by August (including) this year. Additionally, more than 70% of patients have been enrolled for the TALICIA confirmatory Phase III trial in H. pylori infection. Management now expects top-line data from this trial in Q418. We value the company at $404.5m (NIS1.5bn) or $19.0/ADS (NIS6.8/share).