Pluristem Therapeutics — Positive trends in radiation treatment

Pluristem Therapeutics — Positive trends in radiation treatment

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

Price*

US$1.32/ NIS4.67

Market cap

US$127m/ NIS450m

*Priced as at 19 June 2017.

NIS3.58/US$

Net cash ($m) as at 31 March 2017

33.1

Shares in issue

96.3m

Free float

93%

Code

PSTI

Primary exchange

NASDAQ

Secondary exchange

TASE

Share price performance

%

1m

3m

12m

Abs

(3.1)

9.3

(3.1)

Rel (local)

(4.4)

7.0

(17.2)

52-week high/low

$1.7

$1.1

Business description

Pluristem Therapeutics is a biotech company, headquartered in Israel, focused on the development of cell-based therapeutics derived from placenta. The company is advancing PLX-PAD for critical limb ischemia (CLI) in Phase III and has a Phase III study planned for hip fracture. PLX-R18 is being advanced for acute radiation syndrome and hematopoietic cell transplant.

Next events

FNF Phase III initiation

Pending FDA meeting

IC Phase II top-line results

Early 2018

Analysts

Maxim Jacobs

+1 646 653 7027

Nathaniel Calloway

+1 646 653 7036

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*
($m)

EPS*
($)

DPS
($)

P/E
(x)

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.

Exhibit 1: Survival of non-human primates with ARS following PLX-R18 dosing

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)

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

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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US

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Tel Aviv +44 (0)20 3734 1007
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Israel

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

295 Madison Avenue, 18th Floor 10017, New York

US

Sydney +61 (0)2 8249 8342

Level 12, Office 1205

95 Pitt Street, Sydney

NSW 2000, Australia

Tel Aviv +44 (0)20 3734 1007
Medinat Hayehudim 60

Herzilya Pituach, 46766

Israel

Abzena — Focus on integration and growth

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.

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