Pluristem reported data from its pilot study of PLX-R18 for the treatment of acute radiation syndrome (ARS). The study included 48 non-human primates (NHP) who were dosed with 4m, 10m, and 20m cells per kg and showed an improvement in survival to 83%, 86% and 67%, respectively, from 50% in the control arm, although the study was not powered to significance. The company will need to perform a pivotal primate study and a human safety study for approval, which we expect in 2019-20.
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Pluristem Therapeutics |
Positive trends in radiation treatment |
Earnings update |
Pharma & biotech |
20 June 2017 |
Share price performance
Business description
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Pluristem reported data from its pilot study of PLX-R18 for the treatment of acute radiation syndrome (ARS). The study included 48 non-human primates (NHP) who were dosed with 4m, 10m, and 20m cells per kg and showed an improvement in survival to 83%, 86% and 67%, respectively, from 50% in the control arm, although the study was not powered to significance. The company will need to perform a pivotal primate study and a human safety study for approval, which we expect in 2019-20.
Year end |
Revenue ($m) |
PBT* |
EPS* |
DPS |
P/E |
Yield |
06/15 |
0.4 |
(24.7) |
(0.35) |
0.0 |
N/A |
N/A |
06/16 |
2.8 |
(23.2) |
(0.29) |
0.0 |
N/A |
N/A |
06/17e |
0.0 |
(28.9) |
(0.33) |
0.0 |
N/A |
N/A |
06/18e |
0.0 |
(41.5) |
(0.42) |
0.0 |
N/A |
N/A |
Note: *PBT and EPS are normalised, excluding amortisation of acquired intangibles, exceptional items and share-based payments.
ARS data compares favourably to Neupogen
Neupogen is currently stockpiled for hematopoietic recovery following ARS. It was approved for this in 2015 on the basis of a 46-subject NHP study that showed an improvement of survival to 79% from 59% in control (p= 0.023). Also Pluristem stated that PLX-R18 supports the recovery of multiple cell lineages (Neupogen only supports white blood cells), although these data in NHP have not been released.
Benign safety profile could enable simple dosing
Pluristem stated that it did not observe any safety issues with PLX-R18 in healthy primates. This means that the treatment could potentially be administered without concern to a person’s radiation exposure as it would not pose a risk to healthy individuals, compared to Neupogen, which requires frequent blood testing to avoid overdose risk. The ability to indiscriminately dose individuals is a distinct advantage to PLX-R18 in the event of an emergency radiation exposure.
ARS would qualify for a priority review voucher
The legislation regarding the award of priority review vouchers (PRVs) was expanded under the 21st Century Cures Act to include products that address a threat to national security. PLX-R18 should therefore be eligible for such a voucher. The most recent sale of a PRV was for $125m (from Sarepta to Gilead in February 2017), although we expect these prices to drop with the expansion of the program.
Valuation: $169m (NIS603m) or $1.75 (NIS6.26)
We have increased our valuation to $169m (NIS603m) or $1.75 (NIS6.26) per basic share, from $159m (NIS597m) or $1.66 (NIS6.21) per basic share. This adjustment is largely due to including the sale of a priority review voucher for PLX-R18 at $75m in our valuation. The company reported a loss of $7.9m for Q317, up from $6.6m the previous period, due to an increase in R&D spending associated with the PLX-PAD clinical program. We expect the company to require $65m in additional financing to reach profitability in 2020.
Primate data for radiation treatment
Pluristem reported the results from its non-human primate (NHP) study of PLX-R18 for the treatment of acute radiation syndrome (ARS) in early May 2017. The product is being developed for ARS via the FDA animal rule, which allows for approval based on animal studies for conditions such as ARS that cannot be feasibly studied in human clinical trials, so this NHP study is an important component of the approval package. Studies in NHPs are important to establish safety and as the basis for the human dose equivalent, as these animals provide the closest approximation to human subjects, and the purpose of this study was to determine the optimal dose.
The 48 animals were separated into four dosing arms (4, 10, 20 million cells per kilogram, and control) and were either irradiated or left intact. The study saw a trend toward increasing survival in the active arms of the trial: 83%, 86% and 67%, respectively, compared to 50% for the control (Exhibit 1). This “bell shaped” response in which higher doses can have lower efficacy is not uncommon with biologics, and these data provide an important insight into the correct dose to proceed with in future studies. Unfortunately, these data were not powered for statistical significance.
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Exhibit 1: Survival of non-human primates with ARS following PLX-R18 dosing |
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Source: Pluristem Therapeutics |
Importantly, the company also reported that there were no safety issues seen in the non-irradiated group (although detailed safety information was not released), and that leukocyte counts were not increased in these animals. This means that the treatment can potentially be administered before determining the degree of radiation exposure without concern for adverse reactions. The company also stated that PLX-R18 led to improvement in an array of hematopoietic cells, although further details were not provided.
These results compare favourably to Neupogen, which is the currently stockpiled treatment for hematopoietic recovery from ARS. Neupogen showed an improvement in survival to 79% from 59% in the control arm from a study of 46 NHPs (p=0.023).1 On a placebo adjusted basis, Neupogen provided only a 20% improvement in survival compared to 36% for the optimal dose of PLX-R18. Moreover, PLX-R18 could provide a safer and more convenient dosing strategy than Neupogen, if PLX-R18 continues to show a benign safety profile. Neupogen has the potential to induce leucocytosis if overdosed, and requires blood tests every three days to ensure normal white blood cell counts. A drug that can be dosed without risk like PLX-R18 may be beneficial, especially in emergency radiation exposure situations. Finally, Neupogen only improves neutrophil cell counts, whereas the company stated that PLX-R18 improved multiple lineages, which would be a significant improvement over the former, although we would like to see data from NHP to back up these claims.
Neupogen label.
The company will need to perform an additional NHP study that is adequately powered for statistical significance to receive approval for ARS treatment. Additionally, a human safety database must be established, although data from other trials using PLX-R18 (such as the Phase I trial in hematopoietic stem cell transplant patients) can be used. And finally, a human/animal dose conversion study must be performed, which simply requires pharmacokinetic and pharmacodynamic comparisons between humans and animals. We currently model the first potential stockpile contract (for $155m as in previous reports, similar to Neupogen stockpile contracts) in as early as 2020.
An additional upside to the program is that it would qualify Pluristem to receive a priority review voucher (PRV) from the FDA. These vouchers are issued by the FDA to encourage certain development programs such as underserved indications and they allow the voucher holder to shorten the FDA period of review from 10 to six months. PRVs are not attached to a particular company and can be freely traded. In the recent 21st Century Cures Act, the agency expanded the PRV program to include products that are potentially important to national security, and agents used in the event of radiological threats expressly fall under this definition. Therefore, the company should be able to apply for such a voucher in the event that the product gains approval. The most recent voucher sale was for $125m from Sarepta Therapeutics to Gilead in February 2017. These vouchers have been less expensive lately (from a peak of $350m) and we expect prices to continue to trend lower with the recent expansion.
Valuation
We have increased our valuation to $169m (NIS603m) or $1.75 (NIS6.26) per basic share, from $159m (NIS597m) or $1.66 (NIS6.21) per basic share. This adjustment is largely due to including the sale of a priority review voucher for PLX-R18 in our valuation. We currently estimate a preliminary value for the voucher of $75m, although this may change based on how the market for these documents develops. This price is based on the current trend of dropping prices, which we expect to accelerate with an increased number of vouchers issued following passage of the 21st Century Cures Act. We have not increased the probability of success for PLX-R18 for the treatment of ARS at this time due to the lack of statistically significant data and in human safety data. However, we expect to update this in the future when these studies are performed. We have rolled forward our NPVs to Q317 and adjusted for new net cash. Our other assumptions remain unchanged.
Exhibit 2: Valuation of Pluristem
Development program |
Prior data |
Clinical stage |
Prob. of success |
Launch year |
Launch pricing ($) |
Peak sales ($m) |
Patent/exclusivity protection |
Royalty/ margin |
rNPV ($m) |
|
CLI, US |
2x Phase I |
Phase III |
10% |
2021 |
22,500 |
235 |
2036 |
63% |
42.34 |
|
CLI, Europe |
2x Phase I |
Phase III |
10% |
2021 |
13,500 |
247 |
2036 |
59% |
40.14 |
|
CLI, Japan |
2x Phase I |
Phase I/II |
20% |
2021 |
22,500 |
76 |
2036 |
27% |
9.15 |
|
CLI, development costs |
(20.52) |
|||||||||
FNF (US and Europe) |
Phase I for THR |
Phase III ready |
15% |
2021 |
22,100 |
171 |
2036 |
55% |
10.90 |
|
ARS |
Primate studies |
Pivotal primate study |
10-20% |
2020 |
N/A |
155/ contract |
2036 |
77% |
33.74 |
|
IC, US |
N/A |
Phase II |
7.5% |
2022 |
11,500 |
443 |
2036 |
57% |
35.94 |
|
IC, Europe |
N/A |
Phase II |
7.5% |
2022 |
6,900 |
466 |
2036 |
50% |
31.85 |
|
IC, Japan |
N/A |
Phase II |
15% |
2022 |
11,500 |
144 |
2036 |
20% |
6.70 |
|
IC, development costs |
(39.33) |
|||||||||
HCT (US and Europe) |
Mouse studies |
Phase I ready |
5% |
2023 |
29,300 |
239 |
2036 |
61% |
7.93 |
|
Unallocated costs |
(23.36) |
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Total |
|
|
|
|
|
|
|
|
135.48 |
|
Net cash and equivalents (Q317) ($m) |
33.06 |
|||||||||
Total firm value ($m) |
168.54 |
|||||||||
Total basic shares (m, Q317) |
96.3 |
|||||||||
Value per basic share ($) |
$1.75 |
|||||||||
Dilutive warrants from offering (m) |
8.45 |
|||||||||
Diluted firm value ($m) |
180.37 |
|||||||||
Value per diluted share ($) |
$1.72 |
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Source: Pluristem Therapeutics reports, Edison Investment Research
Financials
The company reported a loss of $7.9m for the fiscal Q317 ending 31 March 2017. This is an increase over previous quarters ($6.3m for Q117 and $6.6m in Q217) largely driven by increases in R&D expenses of $6.3m (up from $5.0m in Q117 and $6.2m in Q217). We attribute this increased expense to the completion of enrolment of the intermittent claudication trial that occurred during the quarter. We expect R&D spending to remain at approximately these levels throughout the year ($22.7m total spending), but to increase in later years with the advancement of more programs to late-stage trials. We have made minor adjustments to future R&D spending based on the current run rate. The company completed a bought offering of 14.1m shares and 8.4m warrants (at $1.225) for net proceeds of $15.7m during the quarter. We currently forecast that the company will need $65m in additional financing to reach profitability in 2020.
Exhibit 3: Financial summary
$000s |
2014 |
2015 |
2016 |
2017e |
2018e |
||
Year end 30 June |
US GAAP |
US GAAP |
US GAAP |
US GAAP |
US GAAP |
||
PROFIT & LOSS |
|||||||
Revenue |
|
|
379 |
379 |
2,847 |
0 |
0 |
Cost of Sales |
(11) |
(13) |
(100) |
0 |
0 |
||
Gross Profit |
368 |
366 |
2,747 |
0 |
0 |
||
Research and development |
(19,542) |
(19,173) |
(19,580) |
(22,772) |
(32,153) |
||
Selling, general & administrative |
(8,676) |
(6,460) |
(6,486) |
(6,810) |
(7,151) |
||
EBITDA |
|
|
(29,752) |
(27,341) |
(25,469) |
(31,530) |
(41,187) |
Operating Profit (before GW and except.) |
(27,850) |
(25,267) |
(23,319) |
(29,582) |
(39,303) |
||
Intangible Amortisation |
0 |
0 |
0 |
0 |
0 |
||
Exceptionals/Other |
0 |
0 |
0 |
0 |
0 |
||
Operating Profit |
(27,850) |
(25,267) |
(23,319) |
(29,582) |
(39,303) |
||
Net Interest |
918 |
590 |
73 |
635 |
(2,165) |
||
Other (change in fair value of warrants) |
0 |
0 |
0 |
0 |
0 |
||
Profit Before Tax (norm) |
|
|
(26,932) |
(24,677) |
(23,246) |
(28,947) |
(41,468) |
Profit Before Tax (IFRS) |
|
|
(26,932) |
(24,677) |
(23,246) |
(28,947) |
(41,468) |
Tax |
0 |
0 |
0 |
0 |
0 |
||
Deferred tax |
0 |
0 |
0 |
0 |
0 |
||
Profit After Tax (norm) |
(26,932) |
(24,677) |
(23,246) |
(28,947) |
(41,468) |
||
Profit After Tax (IFRS) |
(26,932) |
(24,677) |
(23,246) |
(28,947) |
(41,468) |
||
Average Number of Shares Outstanding (m) |
63.5 |
70.3 |
79.5 |
87.4 |
99.2 |
||
EPS - normalised (c) |
|
|
(42.40) |
(35.11) |
(29.22) |
(33.10) |
(41.79) |
EPS - IFRS ($) |
|
|
(0.42) |
(0.35) |
(0.29) |
(0.33) |
(0.42) |
Dividend per share (c) |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
||
BALANCE SHEET |
|||||||
Fixed Assets |
|
|
12,036 |
11,287 |
10,345 |
10,023 |
9,832 |
Intangible Assets |
0 |
0 |
0 |
0 |
0 |
||
Tangible Assets |
10,823 |
10,173 |
9,216 |
8,913 |
8,722 |
||
Other |
1,213 |
1,114 |
1,129 |
1,110 |
1,110 |
||
Current Assets |
|
|
61,987 |
56,868 |
35,596 |
29,673 |
24,347 |
Stocks |
0 |
0 |
0 |
0 |
0 |
||
Debtors |
2,263 |
1,691 |
2,228 |
318 |
318 |
||
Cash |
58,819 |
53,119 |
32,750 |
28,134 |
22,808 |
||
Other |
905 |
2,058 |
618 |
1,221 |
1,221 |
||
Current Liabilities |
|
|
(7,397) |
(6,183) |
(5,775) |
(9,765) |
(7,643) |
Creditors |
(7,397) |
(6,183) |
(5,775) |
(9,765) |
(7,643) |
||
Short term borrowings |
0 |
0 |
0 |
0 |
0 |
||
Long Term Liabilities |
|
|
(4,503) |
(3,829) |
(2,010) |
(1,966) |
(36,966) |
Long term borrowings |
0 |
0 |
0 |
0 |
(35,000) |
||
Other long term liabilities |
(4,503) |
(3,829) |
(2,010) |
(1,966) |
(1,966) |
||
Net Assets |
|
|
62,123 |
58,143 |
38,156 |
27,965 |
(10,430) |
CASH FLOW |
|||||||
Operating Cash Flow |
|
|
(19,121) |
(20,605) |
(18,522) |
(18,761) |
(38,634) |
Net Interest |
0 |
0 |
0 |
0 |
0 |
||
Tax |
0 |
0 |
0 |
0 |
0 |
||
Capex |
(1,573) |
(831) |
(1,750) |
(1,750) |
(1,693) |
||
Acquisitions/disposals |
0 |
0 |
0 |
0 |
0 |
||
Financing |
12,624 |
17,201 |
807 |
15,728 |
0 |
||
Dividends |
0 |
0 |
0 |
0 |
0 |
||
Other |
0 |
0 |
0 |
0 |
0 |
||
Net Cash Flow |
(8,070) |
(4,235) |
(19,465) |
(4,783) |
(40,326) |
||
Opening net debt/(cash) |
|
|
(54,213) |
(58,819) |
(53,119) |
(32,750) |
(28,134) |
HP finance leases initiated |
0 |
5 |
0 |
0 |
0 |
||
Exchange rate movements |
0 |
0 |
0 |
0 |
0 |
||
Other |
12,676 |
(1,470) |
(904) |
167 |
0 |
||
Closing net debt/(cash) |
|
|
(58,819) |
(53,119) |
(32,750) |
(28,134) |
12,192 |
Source: Pluristem Therapeutics reports, Edison Investment Research
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Abzena reported solid FY17 results with underlying revenue growth of 41% (to £18.7m). In FY17, Abzena continued to focus on the integration of its service offering across its three sites (US and UK), which has been expanded by its recent placing of £25m gross (issuing 75.8m new shares at 33p). We expect this to enable strong growth and take Abzena to profitability in FY20, which will be a significant milestone for the company. We maintain our valuation at £132m, 62p per share, but note potential upside as it demonstrates growth and as Abzena inside products progress.