corporate presentation july 2019 · corporate presentation july 2019 3 past12 months positive and...

1Corporate Presentation July 2019

Corporate Presentation

July 2019


IMPORTANT NOTICE AND DISCLAIMER

IMPORTANT: You must read the following before continuing. In accessing this document, you agree to be bound by the following terms and conditions.

References herein to this presentation (this “Presentation”) shall mean and include this document, the oral presentation accompanying this document provided by Nanobiotix SA (together withits subsidiaries, the “Group”), any question and answer session following that oral presentation and any further information that may be made available in connection with the subject mattercontained herein (together with the information, statements and opinions contained in this Presentation, the “Information”).

This Presentation has been prepared by Nanobiotix SA and is for information purposes only. The Information is provisional and for information purposes only and is not to be construed asproviding investment advice. The Information is provided as of the date of this Presentation only and may be subject to significant changes at any time without notice. Neither the Group, nor itsadvisors, nor any other person is under any obligation to update the Information. Subject to applicable law, none of the Company or its advisors accepts any responsibility whatsoever and makesno representation or warranty, express or implied, as to the fairness, accuracy, completeness or correctness of the Information. The Information has not been subject to independent verificationand is qualified in its entirety by the business, financial and other information that the Group is require d to publish in accordance with the rules, regulations and practices applicable tocompanies listed on Euronext Paris, including in particular the risk factors in the Company’s Registration Document (Document de Référence) filed with the French Financial Markets Authority(Autorité des marchés financiers – the “AMF”) under number D.17-0470 on April 28, 2017, as well as in its 2017 annual financial report filed with the AMF on March 29, 2018 in any otherperiodic report and in any other press release, which are available free of charge on the websites of the Group (www.nanobiotix.fr) and/or the AMF (www.amf-france.org).

The Information includes information on the use of the Group’s products and its competitive position. Some of the Information is from third parties. While this third party information has beenobtained from sources believed to be reliable, there is no guarantee of the accuracy or completeness of such data. In addition, certain of the industry and market data comes from the Group’sown internal research and estimates based on the knowledge and experience of the Group’s management. While the Group believes that such research and estimates are reasonable and reliable,they, and their underlying methodology and assumptions, have not been verified by any independent source for accuracy or completeness and are subject to change without notice. Accordingly,undue reliance should not be placed on any of the industry, market or competitive position data contained in the Information.

The Information is not directed to, or intended for distribution to or use by, any person or entity that is a citizen or resident of, or located in, any locality, state, country or other jurisdiction wheresuch distribution or use would be contrary to law or regulation or which would require any registration or licensing within such jurisdiction. The Information does not constitute or form part of,and should not be construed as an offer or the solicitation of an offer to subscribe for or purchase of any securities, nor shall there be any sale of these securities in the United States or any otherjurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. No public offering ofsecurities may be conducted in France prior to the delivery by the French Financial Markets Authority of a visa on a prospectus that complies with the provisions of Directive 2003/71/CE asamended. The Information is for information purposes only and does not constitute an offering document or an offer of securities to the public in the United Kingdom to which section 85 of theFinancial Services and Markets Act 2000 of the United Kingdom applies. This Presentation is intended solely for (i) investors in the United States in reliance on the exemption from registrationprovided by Rule 4(a)(2) under the U.S. Securities Act of 1933, as amended (the “Securities Act”) or (ii) to certain non-U.S. persons in offshore transactions outside the United States in relianceon Regulation S under the Securities Act. Securities may not be offered or sold in the United States absent registration under the Securities Act, or an exemption from registration thereunder.

The Information contains certain forward-looking statements. All statements in the Information other than statements of historical fact are or may be deemed to be forward looking statements.These statements are not guarantees of the Group’s future performance. These forward-looking statements relate without limitation to the Group’s future prospects, developments, marketingstrategy regulatory calendar, clinical milestones, assumptions and hypothesis, clinical development approach and financial requirements and are based on analyses of earnings forecasts andestimates of amounts not yet determinable and other financial and non-financial information. Such statements reflect the current view of the Group's management, and are subject to a variety ofrisks and uncertainties as they relate to future events and are dependent on circumstances that may or may not materialize in the future. Forward-looking statements cannot, under anycircumstance, be construed as a guarantee of the Group’s future performance as to strategic, regulatory, financial or other matters, and the Group’s actual performance, including its financialposition, results and cash flow, as well as the trends in the sector in which the Group operates, may differ materially from those proposed or reflected in the forward-looking statements containedin this Presentation. Even if the Group’s performance, including its financial position, results, cash-flows and developments in the sector in which the Group operates were to conform to theforward-looking statements contained in this Presentation, such results or developments cannot be construed as a reliable indication of the Group’s future results or developments. The Groupexpressly declines any obligation to update or to confirm projections or estimates made by analysts or to make public any correction to any prospective information in order to reflect an event orcircumstance that may occur after the date of this Presentation.

http://www.nanobiotix.fr/

http://www.amf-france.org/


Past 12 months

Positive and significant Phase II/III in STS, presented at ASTRO & ESMO

CE Marking in STS

Positive clinical data in STS (IO), H&N Cancer, Liver Cancer presented at major congresses

Completion of Phase I dose escalation in Head and Neck cancers

Positive preclinical in IO showing additional potential of the product in combination with Immune Checkpoint Inhibitors

Clinical trial authorization process to begin in 2H2019 with FDA filing

Major collaboration with MD Anderson to launch nine additional clinical trials

EIB loan granted (EUR 40m) with two tranches already borrowed

Successful ISO certification

Fund raising with US & EU new & existing specialized investors(EUR 29,5m)

Significant global progresses for the company


NANOBIOTIX

Company founded in 2003

Listed on Euronext since 2012

Pioneering Nanomedicine for over 10 years

Developing first-in-class radio enhancer for oncology targeting areas of high unmet needs

Demonstrated clinical Proof of Concept in randomized Phase III trial

Broad ongoing clinical development in 7 clinical trials (targeting ten indications) in EU, US and Asia

Accessing the oncology market with first EU market approval obtained in Soft Tissue Sarcoma

Disruptive technology targeting large unaddressed oncology market


Cancer patients treated with RTx represent significant market opportunity with large unmet medical needs

Source: * World Health Organization (2014); **RADIATION THERAPY EQUIPMENT – A global strategic business report 08/06

Inadequate local control (invasion)

60% RTx**

Inadequate local control (relapse)

Inadequate systemic controlunfavorable safety profile

(dose de-escalation/re-irradiation)

RTx: radiotherapy

Cancer patients

Head and Neck, Glioblastoma, Liver Pancreatic, Rectum, …

Pancreatic, Prostate, Lung, Colorectal, Breast, …

Liver, Lung, Brain, …

Prostate, Head and Neck, Breast, Lung, Brain, Colorectal, …


Nanobiotix targets radiation therapy - one of the largest oncology markets with limited competition

Conventional radiation therapy

Around 60%* of cancer patients receive radiotherapy as a local treatment

Destroys any cancer cell at the right dose

Important limitations due to toxicity on healthy tissues 100 photons @ 6 MeV

20 cm20 cm

50 cm

Xray trackEnergy deposition

How to improve the energy dose within the tumor without damaging healthy tissues?

TUMOR

Source: * RADIATION THERAPY EQUIPMENT – A global strategic business report 08/2006

100 photons at 6 MEV


Our solution: NBTXR3 enhances Xray absorption in the tumor

IP: technology and product candidatesprotected by 20 patent families until at least 2029

Technology key features:

50nm

HfO2 nanoparticles; electron microscopy picture

Designed to strongly

absorb Xrays

Designed to be non-toxic

50 nanometer HfO2* particles were chosenbecause they have the best ratio for X-rayabsorption and non-toxicity

Nanosized to enter cell

* HfO2: Hafnium OxideSource: Maggiorella et al. (2012)

3

2

1


NBTXR3 has a physical mode of action: Leveraging NanoPhysics to fight cancer

Dose

Usual dose delivered in the cell

*Note: Dose enhancement determined by montecarlo simulation (CEA Saclay, France)

Clusters of Nanoparticles

Dose

2 µm

9X Dose*around nanoparticles

Usual dose delivered in the cell

Local absorption of energy

XRay XRay

Radiotherapy Radiotherapy with NBTXR3


NBTXR3 UNIVERSAL MoAtriggering cellular destruction

and adaptative immune response

Clustered Nanoparticles in cytoplasm

large energy deposition in a nano-volume → physical damage

NBTXR3 +RTx

Direct Cell Death (Apoptosis, Necrosis, …)

• Structural Damage• DNA damage• Stress• Immunogenic Cell Death• Sting pathway activationDendritic cell

activation

CD4 & CD8 activation

Tumor Infiltration and Cell Killing


NBTXR3 First in Class Radioenhancer

Physical Mode of Action that could work across all solid tumors to enhance radiotherapy efficacy

Only one administration

Fits into existing standard of careNo change in equipmentNo change in current patient flowNo change in protocol

One product addressing areas of high unmet medical needs

CE Marking obtained in Soft Tissue Sarcoma (commercial name: Hensify®)


A product with solid foundations

Validated & protected productOver 19 patent families across the worldManufacturing demonstrated & certified ISO 13485:2016

Clinical reliabilityUniversal Mechanism of Action (transferability)Proof of Concept demonstrated in a randomized Phase III trial in Soft Tissue SarcomaPositive initial and promising results in different Phase I/II trials (Head and neck, HCC)NBTXR3 has been well toleratedLarge clinical development pipeline with 16 contemplated clinical trials across a broad range of indications

Market acceptance (US & EU)Engaged dialogues with payers across US and EUPreclinical and clinical collaborations with major hospitals, including MD Anderson and Weill CornellMajor clinical collaboration with MD Anderson>400 MDs involved in developmentFitting existing standard of care and single intra-tumoral injection


Pipeline

*Conducted by PharmaEngine

9 Phase I/II or II to be started in:H&N, LAPC, esophageal cancer, NSCLC, Pelvic & LN soft tissue masses

Preclinical PI PII PIIIIndication

NBTXR3

as aSingle Agent

Soft tissue sarcoma

Head and neck cancer(RTx alone)

Liver metastasis

Hepatocellular carcinoma

Rectal cancer*

Prostate cancer

Approval

Head and neck cancer (RTx + chemo)*

NBTXR3

inIO / Combo C

heck

poin

t In

hibi

tors Recurrent

Head & Neck

Lung metastasis

EU / Asia

EU

Asia

EU

Asia

US

US

+NBTXR3

US


First in class product – significant market opportunity to address areas of high unmet medical needs

Product with Physical and Universal Mode of Action Transferability across solid tumors Front line treatment & metastatic treatment

Clinical PoC demonstrated in Soft Tissue Sarcoma Phase II/III CE Marking obtainedPositive Phase II/III New mode of action validated in randomized trialPrimary endpoint: Pathological Complete Response Rate doubled vs radiation alone (p-value = 0.0448)

➔ Target: Start diffusing the product in EU

H&N first indication to be registered in USPositive Phase I data on advanced patientsShowing potential impact on OS, ORR, QoL and well tolerated

➔ Target: Demonstrate the medical value in a high unmet medical needs population

Clinical development in PD-1 resistant patientsPhase I: IND granted in NSCLC & Head and Neck advanced relapsed patient

➔ Target: Demonstrate the value of NBTXR3 in metastatic disease, transforming cold tumors into hot tumors

Expansion of NBTXR3 usage Five ongoing Phase I/II in multiple solid tumorsNine additional clinical development trials planned with MD Anderson global collaboration


NBTXR3 in Soft Tissue Sarcoma


Soft Tissue Sarcoma of the extremities* and trunk wall

Locally advanced soft tissue sarcoma, newly diagnosed or relapsed tumor:

➔High risk tumor➔Borderline unresectable tumor or unfeasible carcinological

surgical resection

Preoperative radiotherapy alone is used as a Standard of Care in this population

Main advantages (long term):• Lower late morbidity (fibrosis, bone fracture, etc.)• Improved long-term functional outcome• Improved quality of life

Unmet medical need for locally advanced soft tissue sarcoma

* Arms and legs

Soft Tissue Sarcoma: patient population


Soft Tissue Sarcoma: treatment objectives

Surgery

Ideal patient outcome in preoperative setting

• Removal of tumor• No remaining tumor cells in the body after surgery

Surgically remove (resect) tumor to improve patients’ survival and quality of life


Phase II/III Study in Soft Tissue Sarcoma

Flowchart and study design

End of treatment

Session of RTx according to standard of care

(25 x 2 Gy)

RTx(89 patients)

Surgery

▪ 180 patients recruited (> 30 sites)▪ 176 treated patients / Intended-to-treat population, full analysis set (ITT-FAS)▪ 4 patients have been excluded from the ITT-FAS (outside of eligibility criteria):

• 3 patients with no sarcoma• 1 patient randomized by error (patient considered as ineligible for pre-operative

radiotherapy by the investigator – untreated patient)

SurgeryDay 1One timeIntratumoral injection

RTx + NBTXR3

(87 patients)

Data presented ASTRO/ESMO 2018


R0 Negative margin

Two important clinical end points in STSPathological response & Surgery Margin

Primary EndpointPathological response*

Secondary Endpoint Surgery (Resection) margin

< 5%

*as per EORTC guidelines (Wardelmann et al., 2016)


NBTXR3 impact on the standard of care (planned radiation and surgery)

*Relative radiation therapy Dose Intensity =(Actual Dose Intensity / Planned Dose Intensity) ITT FAS (Full Analysis Set)

No impact on planned radiation and surgery

No change in Median Relative Radiation therapy dose intensity*

No change in Median Duration of radiotherapy schedule (days)

No change in % of surgery performed

The study confirmed:

• Feasibility of injection

• No change in dosage and schedule of current radiotherapy standard ofcare

• Good local tolerance (similar radiation safety in both arms)

• Manageable acute immunological reaction occurring at the time ofinjection


16,1

7,9

0

2

4

6

8

10

12

14

16

18

Complete Pathological Response

Pathological Complete Response

NBTXR3 activated by radiotherapy (N=87)Radiotherapy alone (N=89)

2x

pCRR: the study met its primary end point

p-value 0.0448*

*Statistically significant at an adjusted α of 0,04575*ITT FAS (Full Analysis Set)

% o

f pat

ient

s w

ith p

CR


pCR multiplied by 4 in high grade sarcoma

Four fold increase in pathological complete response in the NBTXR3 arm in the higher grade sarcoma subgroup

Pathological Complete Response <5% residual viable cancer cells

0

5

10

15

20

25

30

35

% o

f pat

ient

s

1.3

3.9

17.1

3.9

n=15 n=16 n=61 n=61

Grade 1 Grade 2/3

NBTXR3 activated by radiotherapy Radiotherapy alone

4x

ITT Full analysis set – subgroup: patients with pR and known grade% are calculated on the total number of patients in the subgroup. Arm A: 5 missing pR, 6 pts with unknown grade. Arm B: 6 missing pR, 6 pts with unknown grade


NBTXR3 for local and relapse/metastatic treatment of cancerH&N strategy


Head & Neck Cancer

493,000The number of people diagnosed withHead & Neck Cancer in US, EU & Asia-Pacific region each year

ChemoradiationThe standard of care in locallyadvanced Head and Neck Cancer

11%The percentage of patients (i.e. elderlyand/or fragile) that are not eligible for chemoradiation

MAJOR NEED TO IMPROVE SURVIVAL AND QUALITY OF LIFE


H&N: 3 clinical trials to demonstrate value capturing high unmet medical needs

Cancer diagnosis… …Late stage cancer

Radiotherapy alone

NBTXR3-102

1st Line treatment

Radiotherapy +Cisplatin

PEP-503(PharmaEngine)

Checkpoint + NBTXR3

Relapse / Locoregional or

Metastatic

NBTXR3 Monotherapy

Radiotherapy +Nivolumab or

Pembrolizumab

NBTXR3-1100

Local relapseLung MetLiver Met

Can

cer p

atie

nt

path

way

…relapse…


Radiotherapy is the only reasonable option to treat this fragile H&N cancer patient population with limited benefits:

Low ORR, Short PFS, Poor QoL

Poor prognosis patient population:

Stage III and IV

T3 / T4 - Majority of N1 N2

Not eligible for chemo (RTx alone)

> 70 years old, frail

oral cavity, oropharynx

HPV all status (positive & negative)

Ongoing phase I/II in Locally Advanced Squamous Cell Carcinoma of the Oral Cavity or Oropharynx (H&N)


Literature data: NBTXR3 Phase I/II Study Populationhas a poor Overall Survival prognostic

NBTXR3 PI/II patients should have equal or poorer prognosis• Tumor location (Oropharynx & Oral cavity)• Stage III-IV only• >70 years

Amini et al., Cancer May 15, 2016Bourhis et al., Journal of Clinical Oncology, June 2006

Moye et al.,The Oncologist 2015;20:159–165

Amini et al.2016

Moye et al. 2015

Bourhis et al.2006

Median OS at 12-13 months


9 CR, ~90% ORR at highest dosesCR linked to QoL

Depth of best response* (update ICHNO 2019)


No SAEs related to NBTXR3/Well tolerated with no serious side effects observed

100% of disease control at all doses9/11 CR at higher doses* (10%, 15%, 22%)

Median follow up of >20 months

NBTXR3 expected Value in Head and Neck CancerCut-off date: ICHNO 2019

➔ Potential impact on QoL for patients

➔ Potential impact on Survival

* Excluding non-evaluable patients & those recently added in the trial


NBTXR3 in combination with Immune Check Point Inhibitors


H&N: 3 clinical trials to demonstrate value capturing several solid tumor indications

Cancer diagnosis… …Late stage cancer

Radiotherapy alone

NBTXR3-102

1st Line treatment

Radiotherapy +Cisplatin

PEP-503(PharmaEngine)

Checkpoint + NBTXR3

Relapse / Locoregional or

Metastatic

NBTXR3 Monotherapy

Radiotherapy +Nivolumab or

Pembrolizumab

NBTXR3-1100

Local relapseLung MetLiver Met

Can

cer p

atie

nt

path

way

…relapse…


Example ImmunotherapyNivolumab in recurrent patients H&N

Nivolumab: Checkmate 141

Ferris et al. NEJM 2016

Recurrent Head and Neck.

responder

Non responder


Why priming is needed: Many tumors are inadequately responsive to checkpoints & other IO approaches

Hot

Cold

Adapted from Alexandrov et al. (2013) and Gentles et al. (2015)

No infiltration of immune cell

CD8

Limited infiltration of immune cell

Massive infiltration of immune cell

Cold

Hot


Phase I/II in NSCLC & H&N to be initiated in combination with PD-1 Inhibitors

Checkpoint inhibitors refractory patients in NSCLC & H&N

To transform the non responder into

responderwith NBTXR3 and RTx

Nivolumab: Checkmate 141

Ferris et al. NEJM 2016

Recurrent Head and Neck.

responder

Non responder


Phase I Dose Escalation

Cohort 1: Locoregionally recurrent AND metastatic HNSCC

Cohort 3: Patients with liver metastasis pre-treated Primary tumor from NSCLC or HNSCC

Cohort 2: Patients with lung metastasisPrimary tumor from NSCLC or HNSCC

anti PD-1 non responders (pembrolizumab or nivolumab): SD for at least 12 weeks or confirmed PD at 12 weeks


NBTXR3 increases activated CD8 tumor infiltrationPhase III Soft Tissue Sarcoma biomarker data

Biopsy Baseline Pre Treatment

Biopsy Baseline Pre Treatment

Tumor Tissue Post Treatment

Tumor Tissue Post Treatment

RTx + NBTXR3

RTx Alone

Immunorad 2018, Paris, France

-4-3-2-101234567

C D 8

R T a lo n e H f0 2 -N P

a c tiv a te d b y R T

Log2

(fol

d ch

ange

)

log2 ≥16/26 (23%)

log2 ≤18/26 (31%)

log2 ≥111/23 (48%)

log2 ≤14/23 (17%)

-7-6-5-4-3-2-101234567

P D 1

R T a lo n e H f0 2 -N P

a c tiv a te d b y R T

Log2

(fol

d ch

ange

)

log2 ≥19/26 (35%)

log2 ≤111/26 (42%)

log2 ≥19/22 (41%)

log2 ≤15/22 (23%)

PD-1


Global clinical collaboration with MD Anderson: 9 clinical trials planned to start this year

Clinical collaboration will initially support 9 phase I/II or phase II

Multiple indications: head & neck, pancreatic, thoracic, lung, gastrointestinal and genitourinary cancers

Involving around 340 patients

Risk sharing funding scheme: backloaded payment & post FDA registration payment

H&N: Dose Reduction RT for HPV+ OPSCC

H&N: Borderline & Unresectable H&N

H&N:R3+SBRT for inoperable H&N (Re-Irradiation)

H&N:Resected high risk oral cavity/salivary

Pancreas (moonshot program):SBRT+R3 in LAPC

Thoracic:Treatment naïve esophageal cancer

NSCLC:Inoperable, checkpoint inhibitor combination, w/o chemo

NSCLC:Inoperable, checkpoint inhibitor combination, w/ chemo

Pelvic + LN soft tissue masses:Re-Irradiation:


First in class product / addressing high unmet medical needs

• Product with Physical and Universal Mode of Action

• Clinical Proof of Concept demonstrated in Soft Tissue Sarcoma PII/III

• H&N first indication to be registered in US

• Clinical development in PD-1 resistant patients

• Expansion of NBTXR3 usage with 5 ongoing Phase I/II in multiple solid tumors + 9 clinical trials in collaboration with MD Anderson


Many growth levers

Cancer patients

60%RTx

NBTXR3 today is developed in 10 patient populations (+9 with MD Anderson)

& could be expanded to many more patients

*Conducted by PharmaEngine/publication under PharmaEngine responsibility

9 Phase I/II or II to be started in:H&N, LAPC, esophageal cancer, NSCLC, Pelvic & LN soft tissue masses

Preclinical PI PII PIIIIndication

NBTXR3

as aSingle Agent

Soft tissue sarcoma

Head and neck cancer(RTx alone)

Liver metastasis

Hepatocellular carcinoma

Rectal cancer*

Prostate cancer

Approval

Head and neck cancer (RTx + chemo)*

NBTXR3

inIO / Combo C

heck

poin

t In

hibi

tors

RecurrentHead & Neck

Lung metastasis

EU / Asia

EU

Asia

EU

Asia

US

US

+NBTXR3

US


Financials and Shareholders

Analyst Coverage

Financials Shareholding Structure as of June 2019

22,360,039shares

Jefferies – Peter Welford

Kempen – Anastasia Karpova

Gilbert Dupont – Jamila Elbougrini

Kepler Cheuvreux – Arsene Guekam

Stifel – Christian Glennie

H.C. Wainright – Ramakanth Swayampakula

Portzamparc – Christophe Dombu

Degroof Petercam – Benoit Louage

K€ 2018 2017

Total revenue and other income 3,479 3,722

SalesServicesOther salesLicences

Other revenuesResearch Tax CreditSubsidiesOther

116

109

7

-

3,363

3,251

90

22

252

229

23

-

3,470

3,259

154

57

Research & Development (R&D) costs (incl. Share-based payments)

(20,893) (17,733)

Selling, General and Administrative (SG&A) costs (incl. Share-based payments)

(12,653) (11,255)

Operating loss (30,067) (25,267)

Financial loss (277) (876)

Income tax - -

Net loss for the period (30,345) (26,143)

Consolidated cash available as of 30 Jun 2019: €54.9M

46,87%

3,72%4,55%

44,87%

Institutional Investors

Family offices

Management &employees

Retail


Newsflow

H1

H2

✓ MD Anderson clinical collaboration

✓ Preclinical data in IO (NBTXR3 in combination with cPI)

✓ FDA feedback H&N

✓ CE Marking in Europe for STS

✓ Fundraising (EUR 29,5m)

HCC Phase I/II follow up results

Final H&N Phase I dose escalation results

Potential early results IO combination trial

Multiple launch of Phase I/II or II by MD Anderson

US H&N: clinical trial authorization process to begin in 2H2019 with FDA filing

+ other news to come

corporate presentation july 2019 · corporate presentation july 2019 3 past12 months positive and...

Documents