Accumulating data for NBTXR3 and IO combo

Nanobiotix 2 February 2017 Update

Nanobiotix

Accumulating data for NBTXR3 and IO combo

Company update

Pharma & biotech

2 February 2017

Price

€15.5

Market cap

€242m

Net cash (€m) estimate at end-2016

16.8

Shares in issue

15.6m

Free float

40%

Code

NANO

Primary exchange

Euronext Paris

Secondary exchange

N/A

Share price performance

%

1m

3m

12m

Abs

(0.8)

10.6

3.7

Rel (local)

0.8

3.3

9.5

52-week high/low

€19.3

€13.0

Business description

Nanobiotix is a French nanotechnology company developing radiotherapy enhancers for the treatment of cancer. Lead product NBTXR3 is in Phase II/III clinical development in STS in Europe and is partnered with PharmaEngine in Asia Pacific. NBTXR3 is in earlier clinical development in a number of other indications.

Next events

Interim Phase II/III STS data

H117

STS CE mark approval

Mid-2017

Complete H&N cancer data, next steps

H217

Phase I/II prostate cancer data

H217

Analyst

Jonas Peciulis

+44 (0)20 3077 5728

Nanobiotix is a research client of Edison Investment Research Limited

Nanobiotix has made progress with NBTXR3 as a standalone agent to enhance radiation therapy and now has clinical data from three cancers demonstrating consistent safety, feasibility and transferability of effect across different indications. Nanobiotix has also released preclinical results demonstrating NBTXR3’s ability to enhance the immunogenicity of various cancers, which is the cornerstone idea behind the immuno-oncology (IO) products. We expect an eventful 2017, with several clinical trials reporting results and a potential CE mark approval in mid-2017 for use in soft tissue sarcoma (STS). Our valuation has increased to €738m.

Year
end

Revenue (€m)

PBT*
(€m)

EPS*
(€)

DPS
(€)

P/E
(x)

Yield
(%)

12/14

2.8

(9.5)

(0.74)

0.0

N/A

N/A

12/15

4.0

(17.0)

(1.20)

0.0

N/A

N/A

12/16e

5.8

(16.7)

(1.12)

0.0

N/A

N/A

12/17e

5.8

(40.0)

(2.53)

0.0

N/A

N/A

Note: *PBT and EPS are normalised, excluding amortisation of acquired intangibles, exceptional items and share-based payments.

Application for CE mark filed; good H&N cancer data

In August 2016, Nanobiotix filed a CE mark application for NBTXR3. The data package was based on existing evidence obtained in clinical trials so far, including the most advanced registration Phase II/III trial in STS, which is currently ongoing. Evaluation started in September and should last at least nine months. According to the latest update, 115 patients have been randomized into the Phase II/III STS trial and the interim analysis readout is expected in the coming months. In July 2016, Nanobiotix has also presented clinical data from Phase I/II H&N cancer indicating promising signs of tumour response in all treated patients. This was a second indication with clinical data and has demonstrated that NBTXR3’s effect seems to be transferable to other solid tumours given its mechanistic mode of action. More recently, similar positive results were announced from Phase I/II in liver cancers.

Preclinical PoC of ‘hot’ IO and NBTXR3 combo

In line with other researchers Nanobiotix has demonstrated in a number of in vitro and in vivo studies that standalone RT has the potential to act as a vaccine turning the tumour from ‘cold’ to ‘hot’ and activating the host’s immune system to attack it. Nanobiotix’s data show that this effect could be further enhanced with the use of NBTXR3. In our view, this is a natural fit for combination treatment with immuno-oncology products, such as checkpoint inhibitors (anti-PD-1/PD-L1, anti-CTLA-4). While further concrete plans are undisclosed, an obvious strategic direction, in our view, could be early-stage R&D partnerships with companies involved in immuno-oncology, a win-win situation enabled by multiple synergies.

Valuation: Increased to €738.3m or €47.2/share

Our risk-adjusted NPV valuation of Nanobiotix has increased to €738.3m or €47.2/share, from €543m or €34.8/share, due to an increased probability of success for the H&N cancers and rolling our model forward, somewhat offset by a lower net cash position. A forthcoming catalyst-rich period (see next events) will provide a number of value inflection opportunities.

Preclinical proof-of-concept in immuno-oncology

Basis for NBTXR3 positioning in immuno-oncology

Nanobiotix is exploring the potential for its technology to be used in combination with immuno-oncology products, which we described in detail in our last report. The rationale is radiotherapy’s property for amplifying the immune system’s response to the tumour it targets. The core idea behind this is a so-called Immunogenic Cell Death (ICD) effect, which occurs after RT. When radiotherapy (RT) is applied to a tumour locally, the resulting cancerous cell death activates different chain reactions, which in turn amplify the immune system’s response to the tumour itself. In other words, by generating intratumoral ICD, radiotherapy can enhance a tumour’s immunogenicity. This effect is also visible in distant metastases outside the radiation field (abscopal effect). NBTXR3 can enhance the effect of radiation therapy, which theoretically should increase the ICD effect and a tumour’s immunogenicity.

Theoretically, a combination regimen of RT enhanced with Nanobiotix’s NBTXR3 and used alongside immuno-oncology treatment should have a number of synergies, including the fact that many tumours do not elicit an immune response, rendering the IO treatment ineffective. The ICD effect after RT and enhanced with NBTXR3 could potentially turn a ‘cold’ tumour into a ‘hot’ tumour, eliciting or increasing an immune response. Another potential synergy with IO product is the fact that RT is prescribed as early as front-line therapy in some cancers, while IO is still mostly reserved as a late-stage option. A successfully developed NBTXR3-IO product could reach larger populations.

Supporting preclinical data are accumulating

In May and November 2016, Nanobiotix revealed a preclinical dataset demonstrating proof-of-concept in vitro and in vivo:

In in vitro studies Nanobiotix used different cancer cell lines with glioblastoma, colorectal and pancreatic cancers, among others. The cells were exposed to radiation alone (control) and to radiation + NBTXR3. High-mobility group box 1 protein (HMGB1), chaperone calreticulin (CALR) and extracellular adenosine triphosphate (ATP) were selected as markers for ICD. All three represent so-called damage-associated molecular pattern (DAMP) molecules, which have been associated with the ICD effect. Nanobiotix’s data show that higher DAMP levels were observed in all tested cancer cell lines exposed to NBTXR3 + RT versus RT only.

In the in vivo vaccination study (Exhibit 1) mice were injected with colorectal cancer cells, which were irradiated together with the presence of NBTXR3 and without (vaccination stage). The injection was repeated with untreated cancer cells (ie no irradiation) after one week (challenge stage). The response of the immune system was evaluated in terms of how many mice developed tumours. The percentage of tumour-free mice was the highest in the radiation + NBTXR3 group, followed by irradiation only and then by the control groups (cancer cells injected without exposure to radiation or NBTXR3). The results suggest that NBTXR3 enhances the ability of radiotherapy not only to destroy cancerous cells, but also to increase the immunogenicity of the tumour by turning it from ‘cold’ to ‘hot’, ie from ‘invisible’ to the immune system to ‘visible’.

In the in vivo abscopal effect study mice were injected with non-irradiated colorectal cancer cells in both the right and left flanks. Subsequently, once the tumours reached a predefined volume, the right flank tumour was treated with NBTXR3 or the control solution, while the left flank tumour was left untreated. Results demonstrate:

the growth of treated tumours (right flank) was controlled significantly better in the arms treated with RT (NBTXR3 + RT, glucose + RT), which could have been expected (Exhibit 2a);

the growth of untreated tumours (left flank) was significantly delayed in mice that had received NBTXR3 + RT (in the opposite, right flank tumours) compared to the other arms (Exhibit 2b); and

overall survival was significantly prolonged in mice treated with NBTXR3 + RT.

Exhibit 1: In vivo study with NBTXR3 and radiation therapy as vaccination

Source: Nanobiotix

Exhibit 2: Abscopal effect demonstrated by change in tumour volume

Source: Nanobiotix

Exhibit 3: Abscopal effect demonstrated by overall survival

Source: Nanobiotix. Note: *NBTXR3 + RT versus glucose + RT: p<0.05.

Next steps

The successful advance of immuno-oncology products has given a whole new perspective on the ICD effect. A recent review published by Kang et al identified more than 90 ongoing clinical trials registered on clinicaltrials.gov that explore the combination of various immuno-oncology treatments and RT. In our view, this clearly shows recognition by the industry of the importance of RT, due not only to its conventional ‘mechanistic’ action against cancer, but also to its immunogenic effect. Since most of the trials are still early (Phase I/II), the final conclusions on how to position RT with IO products are still to come. Meanwhile, Nanobiotix’s new preclinical data indicate that, due to synergies, NBTXR3 could be a natural fit in the RT+IO setting. Nanobiotix has not disclosed further specific plans yet but, in our view, an obvious strategic direction could be early-stage R&D partnerships with companies involved in the immuno-oncology space. An attractive aspect of such a strategy is that these combination products would exploit the radiation therapy benefit and potentially allow for new patent applications, although so far RT has not been patentable.

Data pave the way for registration trial in H&N cancer

In July 2016, Nanobiotix announced positive results from its Phase I/II trial with H&N cancer patients. This is now the second indication with clinical data for NBTXR3 and, importantly, demonstrates that NBTXR3’s effect seems to be transferable to other solid tumours given its mechanistic mode of action.

Phase I/II design and endpoints

The trial was a Phase I/II prospective, open-label, non-randomised, multi-centre, dose escalation trial with H&N cancer patients who had locally advanced squamous cell carcinoma of the oral cavity, tongue or throat. Notably, these were frail and elderly patients with a poorer prognosis than the similar H&N cancer population and were not fit for standard of care with a combination treatment involving radiotherapy (RT) and chemotherapy, and therefore underwent RT only.

The trial enrolled 10 patients, seven of whom were evaluable (two were not evaluable and assessment of patient number 10 was ongoing at the time). Exhibit 4 shows the design of the Phase I/II H&N cancer trial. Initially, two administration routes were planned: intratumoral and selective intra-arterial (which feeds the tumour), but as the intratumoral injection was shown to be feasible, the intra-arterial route was not explored. The patients were administered with increasing dose levels from 5% to 22% of the tumour volume (the 10% dose was optimal in the lead Phase II/III trial for STS). After a single injection of NBTXR3, the patients received standard-of-care RT (70Gy divided into 35 daily fractions). After the patients accumulated c 70% (50Gy) of the total required radiation dose, the tumour reduction was assessed to decide whether continuing the RT was worthwhile (if tumour shrinkage was more than 50%) or, if the response was not sufficient, the patients were offered salvage surgery.

Exhibit 4: Design and clinical endpoints of the Phase I/II H&N cancer study

Source: Nanobiotix

Results

Primary endpoints – safety profile confirmed

The safety profile (the primary endpoint) was excellent, with no adverse events related to NBTXR3, and only one patient experienced a grade 1 injection site reaction. Other adverse events were related to RT, the disease itself or comorbidities. The feasibility of the NBTXR3 injection was demonstrated with the first three dose levels, while the recruitment for the 22% level is ongoing. Importantly, no leakage to surrounding healthy tissue was observed.

Secondary endpoints

Tumour response was a secondary endpoint, measured with changes in volume and the longest dimension on MRI scans (RECIST 1.1 criteria), which were evaluated after the patients received 50Gy and the full dose of 70Gy at the end of the treatment. Long-term secondary endpoints are overall survival (OS), local progression-free survival (LPFS) and progression-free survival (PFS). OS, PFS and LPFS will be established during a follow-up period.

Exhibit 5: Average tumour volume reduction in seven evaluated patients after 50Gy (71%) and 70Gy (full dose)

Source: Nanobiotix

Seven patients were evaluated, all of whom demonstrated a tumour response of 50% or greater, with two patients achieving complete or near-complete shrinkage. During the follow-up LPFS, PFS and OS will be established, which will allow a more detailed comparison with the historical data, but a complete response already looks promising. Adelstein et al.1 published results from one of the earlier clinical studies that sought to explore the effect of a combination treatment with radiotherapy and chemotherapy, which is standard of care now. In a standalone radiotherapy arm (n = 95) with the treatment schedule comparable to Nanobiotix’s study, a complete response was seen in 27.4% patients. Notably, these patients were eligible for chemotherapy treatment, thus were likely on average to be healthier than patients in the Nanobiotix trial. This, together with the fact that all treated patients in Nanobiotix’s study showed a tumour response, validates further exploration of NBTXR3 for H&N cancer, in our view.

D. Adelstein et al. An Intergroup Phase III Comparison of Standard Radiation Therapy and Two Schedules of Concurrent Chemoradiotherapy in Patients with Unresectable Squamous Cell Head and Neck Cancer. J Clin Oncol. 2003 Jan 1;21(1):92-8.

Next steps

Based on its positive Phase I/II study, Nanobiotix is now planning a Phase II/III study which, if positive, would allow for registration, which we assume in 2019 in our model. The details are yet to be announced.

As announced in October 2016, Nanobiotix’s partner PharmaEngine has launched a second clinical trial in Asia that will enrol H&N cancer patients (the seventh trial with NBTXR3 in total). The Asian partner is already running a Phase I/II in rectal cancer. The new H&N cancer trial will evaluate optimal dose and safety. While this follows the successful study conducted by Nanobiotix in Europe, PharmaEngine will target a larger H&N population, which will include all patients receiving both chemotherapy and radiotherapy. This will broaden the target population and should provide additional insights to Nanobiotix while it prepares for the registration Phase II/III trial in Europe.

Liver cancers – third indication with clinical data

In December 2016, Nanobiotix announced preliminary feasibility and safety data from Phase I/II trials in liver cancers (HCC and metastases). This is now a third indication with clinical data. While specific patient numbers were not disclosed, Nanobiotix confirmed that the dose of 10% of the tumour volume was feasible and safe including no changes in liver function in both HCC and metastasis patient populations. No leakage outside the tumour has been detected. The study is now recruiting patients for the higher dose arm, but the 10% dose level was described as the most optimal in terms of efficacy and local mass effect in the most advanced STS trial. Phase II part of the study will also explore initial efficacy, eg complete response rate, progression free survival and overall survival. To us, the importance of this preliminary analysis is that the findings were similar to the more advanced trials (STS and H&N cancer) and again supported the idea of NBTXR3’s effect being transferable to other solid tumours given its mechanistic mode of action.

Valuation

Our risk-adjusted NPV valuation of Nanobiotix has increased to €738.3m or €47.2/share, from €543m or €34.8/share, due to an increased probability of success for the H&N cancer indication and rolling our model forward, somewhat offset by a lower net cash position. The main change is the increase in the probability of success for the H&N cancer indication from 45% to 60%, which reflects the likelihood of reaching the market, in line with the most advanced STS indication.

Previously PharmaEngine indicated that they could expand beyond rectal cancer, although did not disclose specific indications. At that time, we assumed four additional indications for PharmaEngine – STS, rectal, oesophageal and liver cancers – in our valuation. We replace the oesophageal cancer indication in our model with H&N cancer, as we see the expansion as in line with the original development plan. However, the valuation was not significantly affected due to a similar calculated market potential.

H&N cancer data de-risks the pipeline

Currently NBTXR3 is being investigated for a total of six indications in seven clinical trials. Nanobiotix is running STS (Europe/Asia; Phase II/III; with PharmaEngine), prostate cancer (US, Phase I/II), liver cancers (Europe; HCC and metastases; Phase I/II), H&N cancer (Europe; Phase I/II), while PharmaEngine runs two more trials in Asia for rectal cancer (Phase I/II) and H&N cancer (Phase I/II).

Exhibit 6: Nanobiotix rNPV valuation

Product

Indication

Launch

Peak sales (€m)

NPV
(€m)

Probability

rNPV
(€m)

rNPV/share (€/share)

NBTXR3 – US/Europe

STS

2017

220

303.6

60%

182.2

11.7

Head & neck cancer

2019

380

403.1

60%

239.0

15.3

Liver cancers including liver mets

2021

500

345.1

45%

146.0

9.3

Prostate cancer

2022

400

277.4

45%

118.9

7.6

NBTXR3 – Asia

STS, H&N, rectal, liver cancers

2017

440

67.7

45%

30.5

1.9

Estimate net cash (at end 2016)

21.8

100%

21.8

1.4

Valuation

 

 

 

1,418.7

738.3

47.2

Source: Edison Investment Research. Note: 12.5% discount rate used.

In valuing Nanobiotix, we use an accelerated de-risking approach, which we discussed in detail in our previous report. H&N cancer is the second tumour type with positive Phase I/II clinical data, indicating that the effect of NBTXR3 is potentially transferable to other types of tumours due to the fact that this is simply a nanoparticle (coated hafnium oxide) injection. This leads us to increase the probabilities for other indications that are still in Phase I/II from 40% to 45% and results in subsequent increases in the rNPVs.

Financials

Nanobiotix posted its Q316 revenues with licence-related income of €1.0m for 9M16, while more detailed H116 results showed that total operating expenses were €13.1m, in line with our expectations. We estimate total opex of €22.5m for FY16. Nanobiotix received an interest-free loan, repayable from September 2019, of €2m from Bpifrance (formerly OSEO). Given the CE mark review timeline of at least nine months and a potential approval by mid-2017 in a best case scenario, we lower our expected 2017 sales in Europe and the associated marketing costs. By end-2016 we estimate total debt of €6.4m and net cash of €21.8m, significantly boosted by a fund-raise in March 2016, resulting in €22.2m gross. According to our model, cash should be sufficient to fund operations well into 2017, assuming that development continues in all planned indications. For the purpose of our model, we include illustrative long-term debt of c €11.9m, assuming that all projects can be fully supported with this in 2017.

Exhibit 7: Financial summary

€'000s

2010

2011

2012

2013

2014

2015

2016e

2017e

December

IFRS

IFRS

IFRS

IFRS

IFRS

IFRS

IFRS

IFRS

PROFIT & LOSS

Revenue

 

 

1,135

1,360

971

1,595

2,771

4,015

5,789

5,806

Cost of Sales

0

0

0

0

0

0

0

(161)

Gross Profit

1,135

1,360

971

1,595

2,771

4,015

5,789

5,646

Research and development

(4,186)

(5,213)

(4,312)

(6,026)

(8,076)

(13,902)

(15,000)

(37,000)

EBITDA

 

 

(3,935)

(5,030)

(5,006)

(7,945)

(9,312)

(16,686)

(16,323)

(39,147)

Operating Profit (before amort. and except.)

(4,092)

(5,213)

(5,146)

(8,171)

(9,605)

(17,132)

(16,673)

(39,522)

Intangible Amortisation

(4)

(14)

(7)

(8)

(15)

(10)

(11)

(11)

Exceptionals

0

0

0

0

0

0

0

0

Other

(0)

(0)

(22)

0

2

15

0

0

Operating Profit

(4,096)

(5,227)

(5,175)

(8,179)

(9,618)

(17,127)

(16,683)

(39,533)

Net Interest

11

(19)

(77)

34

141

124

(9)

(432)

Profit Before Tax (norm)

 

 

(4,081)

(5,233)

(5,223)

(8,137)

(9,464)

(17,008)

(16,681)

(39,954)

Profit Before Tax (reported)

 

 

(4,086)

(5,247)

(5,252)

(8,145)

(9,477)

(17,003)

(16,692)

(39,965)

Tax

0

0

(79)

18

(79)

0

0

0

Profit After Tax (norm)

(4,081)

(5,233)

(5,324)

(8,118)

(9,541)

(16,993)

(16,681)

(39,954)

Profit After Tax (reported)

(4,086)

(5,247)

(5,331)

(8,126)

(9,557)

(17,003)

(16,692)

(39,965)

Average Number of Shares Outstanding (m)

6.8

7.7

8.2

10.8

12.9

14.1

14.9

15.8

EPS - normalised (€)

 

 

(0.60)

(0.68)

(0.65)

(0.75)

(0.74)

(1.20)

(1.12)

(2.53)

EPS - normalised and fully diluted (€)

 

(0.60)

(0.68)

(0.65)

(0.75)

(0.74)

(1.20)

(1.12)

(2.53)

EPS - (reported) (€)

 

 

(0.60)

(0.68)

(0.65)

(0.76)

(0.74)

(1.20)

(1.12)

(2.53)

Dividend per share (€)

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

Gross Margin (%)

100.0

100.0

100.0

100.0

100.0

100.0

100.0

97.2

EBITDA Margin (%)

N/A

N/A

N/A

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

N/A

N/A

N/A

BALANCE SHEET

Fixed Assets

 

 

682

580

485

545

1,549

3,470

3,378

3,261

Intangible Assets

2

7

0

9

10

8

5

1

Tangible Assets

638

511

416

468

1,292

2,432

2,342

2,229

Investments

42

63

69

68

247

1,031

1,031

1,031

Current Assets

 

 

7,253

2,333

13,539

6,894

35,505

22,948

34,108

6,994

Stocks

0

0

0

0

0

0

0

13

Debtors

0

0

1

1

2

80

115

116

Cash

649

899

12,361

5,002

32,986

17,003

28,128

1,000

Other

6,604

1,434

1,177

1,891

2,517

5,865

5,865

5,865

Current Liabilities

 

 

(1,539)

(1,415)

(2,160)

(3,282)

(4,424)

(7,102)

(10,659)

(3,433)

Creditors

(1,349)

(1,119)

(1,800)

(3,051)

(4,103)

(6,032)

(9,589)

(2,425)

Short term borrowings

(190)

(295)

(360)

(231)

(321)

(1,070)

(1,070)

(1,008)

Long Term Liabilities

 

 

(505)

(573)

(1,167)

(975)

(2,314)

(3,705)

(5,468)

(24,136)

Long term borrowings

(474)

(527)

(1,072)

(875)

(2,002)

(3,531)

(5,281)

(16,942)

Other long term liabilities

(31)

(46)

(95)

(100)

(312)

(174)

(187)

(7,194)

Net Assets

 

 

5,891

926

10,697

3,182

30,315

15,611

21,359

(17,314)

CASH FLOW

Operating Cash Flow

 

 

(4,157)

(4,862)

(3,786)

(6,837)

(8,573)

(16,843)

(11,497)

(38,026)

Net Interest

13

(7)

(119)

(18)

(48)

432

(9)

(432)

Tax

0

0

0

0

0

0

0

0

Capex

(245)

(60)

(45)

(196)

(963)

(1,495)

(261)

(261)

Acquisitions/disposals

0

0

1

4

0

73

(8)

(8)

Financing

8,011

15

14,807

14

36,532

355

21,148

0

Dividends

0

0

0

0

0

0

0

0

Net Cash Flow

3,621

(4,914)

10,858

(7,034)

26,947

(17,478)

9,375

(38,727)

Opening net debt/(cash)

 

 

(396)

15

(76)

(10,929)

(3,895)

(30,663)

(12,402)

(21,777)

HP finance leases initiated

0

0

0

0

0

0

0

0

Other

(4,033)

5,006

(5)

0

(179)

(784)

0

0

Closing net debt/(cash)

 

 

15

(76)

(10,929)

(3,895)

(30,663)

(12,402)

(21,777)

16,950

Source: Nanobiotix accounts, Edison Investment Research

Edison, the investment intelligence firm, is the future of investor interaction with corporates. Our team of over 100 analysts and investment professionals work with leading companies, fund managers and investment banks worldwide to support their capital markets activity. We provide services to more than 400 retained corporate and investor clients from our offices in London, New York, Frankfurt and Sydney. Edison is authorised and regulated by the Financial Conduct Authority. Edison Investment Research (NZ) Limited (Edison NZ) is the New Zealand subsidiary of Edison. Edison NZ is registered on the New Zealand Financial Service Providers Register (FSP number 247505) and is registered to provide wholesale and/or generic financial adviser services only. Edison Investment Research Inc (Edison US) is the US subsidiary of Edison and is regulated by the Securities and Exchange Commission. Edison Investment Research Limited (Edison Aus) [46085869] is the Australian subsidiary of Edison and is not regulated by the Australian Securities and Investment Commission. Edison Germany is a branch entity of Edison Investment Research Limited [4794244]. www.edisongroup.com

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Copyright 2017 Edison Investment Research Limited. All rights reserved. This report has been commissioned by Nanobiotix and prepared and issued by Edison for publication globally. All information used in the publication of this report has been compiled from publicly available sources that are believed to be reliable, however we do not guarantee the accuracy or completeness of this report. Opinions contained in this report represent those of the research department of Edison at the time of publication. The securities described in the Investment Research may not be eligible for sale in all jurisdictions or to certain categories of investors. This research is issued in Australia by Edison Aus and any access to it, is intended only for "wholesale clients" within the meaning of the Australian Corporations Act. The Investment Research is distributed in the United States by Edison US to major US institutional investors only. Edison US is registered as an investment adviser with the Securities and Exchange Commission. Edison US relies upon the "publishers' exclusion" from the definition of investment adviser under Section 202(a)(11) of the Investment Advisers Act of 1940 and corresponding state securities laws. As such, Edison does not offer or provide personalised advice. We publish information about companies in which we believe our readers may be interested and this information reflects our sincere opinions. The information that we provide or that is derived from our website is not intended to be, and should not be construed in any manner whatsoever as, personalised advice. Also, our website and the information provided by us should not be construed by any subscriber or prospective subscriber as Edison’s solicitation to effect, or attempt to effect, any transaction in a security. The research in this document is intended for New Zealand resident professional financial advisers or brokers (for use in their roles as financial advisers or brokers) and habitual investors who are “wholesale clients” for the purpose of the Financial Advisers Act 2008 (FAA) (as described in sections 5(c) (1)(a), (b) and (c) of the FAA). This is not a solicitation or inducement to buy, sell, subscribe, or underwrite any securities mentioned or in the topic of this document. This document is provided for information purposes only and should not be construed as an offer or solicitation for investment in any securities mentioned or in the topic of this document. A marketing communication under FCA Rules, this document has not been prepared in accordance with the legal requirements designed to promote the independence of investment research and is not subject to any prohibition on dealing ahead of the dissemination of investment research.
Edison has a restrictive policy relating to personal dealing. Edison Group does not conduct any investment business and, accordingly, does not itself hold any positions in the securities mentioned in this report. However, the respective directors, officers, employees and contractors of Edison may have a position in any or related securities mentioned in this report. Edison or its affiliates may perform services or solicit business from any of the companies mentioned in this report. The value of securities mentioned in this report can fall as well as rise and are subject to large and sudden swings. In addition it may be difficult or not possible to buy, sell or obtain accurate information about the value of securities mentioned in this report. Past performance is not necessarily a guide to future performance. Forward-looking information or statements in this report contain information that is based on assumptions, forecasts of future results, estimates of amounts not yet determinable, and therefore involve known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of their subject matter to be materially different from current expectations. For the purpose of the FAA, the content of this report is of a general nature, is intended as a source of general information only and is not intended to constitute a recommendation or opinion in relation to acquiring or disposing (including refraining from acquiring or disposing) of securities. The distribution of this document is not a “personalised service” and, to the extent that it contains any financial advice, is intended only as a “class service” provided by Edison within the meaning of the FAA (ie without taking into account the particular financial situation or goals of any person). As such, it should not be relied upon in making an investment decision. To the maximum extent permitted by law, Edison, its affiliates and contractors, and their respective directors, officers and employees will not be liable for any loss or damage arising as a result of reliance being placed on any of the information contained in this report and do not guarantee the returns on investments in the products discussed in this publication. FTSE International Limited (“FTSE”) © FTSE 2017. “FTSE®” is a trade mark of the London Stock Exchange Group companies and is used by FTSE International Limited under license. All rights in the FTSE indices and/or FTSE ratings vest in FTSE and/or its licensors. Neither FTSE nor its licensors accept any liability for any errors or omissions in the FTSE indices and/or FTSE ratings or underlying data. No further distribution of FTSE Data is permitted without FTSE’s express written consent.

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

245 Park Avenue, 39th Floor

10167, New York

US

Sydney +61 (0)2 9258 1161

Level 25, Aurora Place

88 Phillip St, Sydney

NSW 2000, Australia

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

245 Park Avenue, 39th Floor

10167, New York

US

Sydney +61 (0)2 9258 1161

Level 25, Aurora Place

88 Phillip St, Sydney

NSW 2000, Australia

Edison, the investment intelligence firm, is the future of investor interaction with corporates. Our team of over 100 analysts and investment professionals work with leading companies, fund managers and investment banks worldwide to support their capital markets activity. We provide services to more than 400 retained corporate and investor clients from our offices in London, New York, Frankfurt and Sydney. Edison is authorised and regulated by the Financial Conduct Authority. Edison Investment Research (NZ) Limited (Edison NZ) is the New Zealand subsidiary of Edison. Edison NZ is registered on the New Zealand Financial Service Providers Register (FSP number 247505) and is registered to provide wholesale and/or generic financial adviser services only. Edison Investment Research Inc (Edison US) is the US subsidiary of Edison and is regulated by the Securities and Exchange Commission. Edison Investment Research Limited (Edison Aus) [46085869] is the Australian subsidiary of Edison and is not regulated by the Australian Securities and Investment Commission. Edison Germany is a branch entity of Edison Investment Research Limited [4794244]. www.edisongroup.com

DISCLAIMER
Copyright 2017 Edison Investment Research Limited. All rights reserved. This report has been commissioned by Nanobiotix and prepared and issued by Edison for publication globally. All information used in the publication of this report has been compiled from publicly available sources that are believed to be reliable, however we do not guarantee the accuracy or completeness of this report. Opinions contained in this report represent those of the research department of Edison at the time of publication. The securities described in the Investment Research may not be eligible for sale in all jurisdictions or to certain categories of investors. This research is issued in Australia by Edison Aus and any access to it, is intended only for "wholesale clients" within the meaning of the Australian Corporations Act. The Investment Research is distributed in the United States by Edison US to major US institutional investors only. Edison US is registered as an investment adviser with the Securities and Exchange Commission. Edison US relies upon the "publishers' exclusion" from the definition of investment adviser under Section 202(a)(11) of the Investment Advisers Act of 1940 and corresponding state securities laws. As such, Edison does not offer or provide personalised advice. We publish information about companies in which we believe our readers may be interested and this information reflects our sincere opinions. The information that we provide or that is derived from our website is not intended to be, and should not be construed in any manner whatsoever as, personalised advice. Also, our website and the information provided by us should not be construed by any subscriber or prospective subscriber as Edison’s solicitation to effect, or attempt to effect, any transaction in a security. The research in this document is intended for New Zealand resident professional financial advisers or brokers (for use in their roles as financial advisers or brokers) and habitual investors who are “wholesale clients” for the purpose of the Financial Advisers Act 2008 (FAA) (as described in sections 5(c) (1)(a), (b) and (c) of the FAA). This is not a solicitation or inducement to buy, sell, subscribe, or underwrite any securities mentioned or in the topic of this document. This document is provided for information purposes only and should not be construed as an offer or solicitation for investment in any securities mentioned or in the topic of this document. A marketing communication under FCA Rules, this document has not been prepared in accordance with the legal requirements designed to promote the independence of investment research and is not subject to any prohibition on dealing ahead of the dissemination of investment research.
Edison has a restrictive policy relating to personal dealing. Edison Group does not conduct any investment business and, accordingly, does not itself hold any positions in the securities mentioned in this report. However, the respective directors, officers, employees and contractors of Edison may have a position in any or related securities mentioned in this report. Edison or its affiliates may perform services or solicit business from any of the companies mentioned in this report. The value of securities mentioned in this report can fall as well as rise and are subject to large and sudden swings. In addition it may be difficult or not possible to buy, sell or obtain accurate information about the value of securities mentioned in this report. Past performance is not necessarily a guide to future performance. Forward-looking information or statements in this report contain information that is based on assumptions, forecasts of future results, estimates of amounts not yet determinable, and therefore involve known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of their subject matter to be materially different from current expectations. For the purpose of the FAA, the content of this report is of a general nature, is intended as a source of general information only and is not intended to constitute a recommendation or opinion in relation to acquiring or disposing (including refraining from acquiring or disposing) of securities. The distribution of this document is not a “personalised service” and, to the extent that it contains any financial advice, is intended only as a “class service” provided by Edison within the meaning of the FAA (ie without taking into account the particular financial situation or goals of any person). As such, it should not be relied upon in making an investment decision. To the maximum extent permitted by law, Edison, its affiliates and contractors, and their respective directors, officers and employees will not be liable for any loss or damage arising as a result of reliance being placed on any of the information contained in this report and do not guarantee the returns on investments in the products discussed in this publication. FTSE International Limited (“FTSE”) © FTSE 2017. “FTSE®” is a trade mark of the London Stock Exchange Group companies and is used by FTSE International Limited under license. All rights in the FTSE indices and/or FTSE ratings vest in FTSE and/or its licensors. Neither FTSE nor its licensors accept any liability for any errors or omissions in the FTSE indices and/or FTSE ratings or underlying data. No further distribution of FTSE Data is permitted without FTSE’s express written consent.

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

245 Park Avenue, 39th Floor

10167, New York

US

Sydney +61 (0)2 9258 1161

Level 25, Aurora Place

88 Phillip St, Sydney

NSW 2000, Australia

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

245 Park Avenue, 39th Floor

10167, New York

US

Sydney +61 (0)2 9258 1161

Level 25, Aurora Place

88 Phillip St, Sydney

NSW 2000, Australia

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