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Physical Mode of Action broadly applicable across multiple solid tumor indications 60% of patients receive radiotherapy

Positive preliminary results in four other clinical trials Robust intellectual property and established manufacturing facility with substantial production capacity First market approval in Europe in Soft Tissue Sarcoma (STS)

Positive Head & Neck (H&N) Phase I trial with potential impact on OS and QoL US FDA Fast Track designation obtained in February 2020 First positive data of expansion trial presented at ASCO in May 2020 US FDA safe-to-proceed for Phase III protocol in June 2020

Short term evaluation of potential clinical value in Immuno-Oncology Nine clinical trials in collaboration with MD Anderson with first patient to be treated in pancreatic cancer Upcoming end of clinical trials (PE trials in H&N and rectum) and new readout in H&N and liver trials

RECEIVING RTx NUMBER OF PATIENTS W/RTx 87% Breast cancer 1,800,000 77% Lung cancer 1,600,000 74% H&N 700,000 60% 58% Prostate 740,000 18M RTx 60% Rectum 420,000 new patients 49% Pancreas 225,000 per year 80% CNS 237,000 diagnosed … … with cancer worldwide

Source: World Health Organization (2014); EQUIPMENT – A global strategic business report 08/06 ; Delaney et al. 2015; Globocan 2018. Inadequate local control (Local invasion or systemic expansion)

Inadequate systemic control 60% (metastatic patients) 18M RTx Unfavorable safety profile new patients (dose de-escalation/re-irradiation) per year diagnosed with cancer worldwide

Source: World Health Organization (2014); RADIATION THERAPY EQUIPMENT – A global strategic business report 08/06 ; Delaney et al. 2015; Globocan 2018.

• First-in-class radioenhancer

• Aqueous suspension of inorganic crystalline hafnium oxide (HfO2)

• Nanosized to enter the cell and designed to strongly absorb ionizing radiation Dose Dose

dose* around nanoparticles Usual dose delivered Radiotherapy in the cell Radiotherapy with NBTXR3 Usual dose delivered in the cell

Clusters of XRay XRay Nanoparticles

Local absorption 2 µm of energy

*Dose enhancement determined by Monte Carlo simulation (CEA Saclay, France). NBTXR3’s UNIVERSAL, PHYSICAL MOA triggers cellular destruction along with potential adaptative immune response.

Physical damage inducing Direct Cell Death (Apoptosis, Necrosis, …) • Structural Damage • DNA damage • Stress • Immunogenic Cell Death Cell Killing by • Sting pathway activation CD8/CD4 activation

Source: Marril et al, Radiother Oncol, 2019

Clinical Proof of Concept established in a randomized Phase III & marketing approval received in the EU. A defined pathway to market in the US & EU with an aim for high medical & economical value creation. European Expansion through multiple ongoing or planned Phase I/II trials. Received Nanobiotix Trials

PharmaEngine Trials

Global MDA Trials Phase Phase III to be launched Validated EU Expansion Phase I EU US US Asia Asia Phase ongoing Phase Phase Phase Phase Phase

I/II I/II I/II I/II I/II

be be be

EU ongoing ongoing ongoing ongoing ongoing be

To To To To

Phase I To

Safe to to Safe to Safe to Safe

Validated to Safe

proceed proceed proceed proceed

Ongoing

launched

Launched Launched Validated Launched

HCC IO H&N Lung Advanced Under Under Soft Tissue Sarcoma Head & Neck Prostate Rectum H&N Pancreas Esoph. Lung2 H&N1 H&N2 Liver mets Lung reirradiation tumors discussion discussion

• High risk tumor • Borderline unresectable tumor or unfeasible carcinological surgical resection • Preoperative radiotherapy alone is the Standard of Care Soft Tissue Sarcoma (STS) of Primary endpoint: the Extremity and Trunk wall • Pathological complete response rate4 (pCRR) following EORTC Guidelines5 Key inclusion criteria Arm A NBTXR31 activated • Age ≥ 18 years-old Secondary endpoints: by EBRT2 R • Safety • Locally advanced STS of the 1:1 • Carcinologic resection (surgical margin, R0, …) extremity and trunk wall, newly Arm B 2 • Pathological Response (pR) diagnosed or relapsed tumor EBRT alone • Amputation rate • High-risk tumor N=180 randomized3 • Unresectable tumor or unfeasible Stratification: carcinological surgical resection 32 sites in 11 • Myxoid liposarcoma / other countries in Europe • WHO score of 0 to 2 and Asia

1 IT injection of a dose, 10% of baseline tumor volume 2 50 Gy, 25 fractions x 2 Gy, over 5 weeks 3 4 patients excluded from the ITT Full analysis set : 3 did not have STS (2 in Arm A, 1 in Arm B), 1 (in Arm A) was not eligible for preoperative RT 4 Pathological Response evaluated by an independent central Pathological Review Board 5 Wardelmann E et al, Eur J Cancer, 2016 Cf Clinicaltrials.gov - NCT01433068 Pathological Complete Response

20, p-value 0.0448* NBTXR3 activated by radiotherapy (N=87) 16,1 Radiotherapy alone (N=89) 15,

X2

10,

7,9 % of % of patients pCR with

5,

0, Complete Pathological Response

180 patients / RTx vs RTx+NBTXR3 *pCRR = Pathological Complete Response Rate Primary Endpoint pCRR* x2 in ITT FAS** population **ITT FAS = Intention To Treat Full Analysis Set; statistically significant at α threshold of 0.04575 Source: Bonvalot et al, Lancet Oncol, 2019 Pathological Complete Response <5% residual viable cancer cells

20, 17,1

15,

X4

10, % % ofpatients

5, 3,9 3,9 1,3

0, n=15 n=16 n=61 n=61 Grade 1 Grade 2/3

NBTXR3 activated by radiotherapy Radiotherapy alone Source: Bonvalot et al, Lancet Oncol, 2019 p-value 0.0424* 35, p-value 0.0140* 80,

77,0 28,8

26,3 75,

tumor 19,2

17,5

70, infarction

/ necrosis

% % with ofpatients 8,8

65, 64,0 % of % of patients R0 margins withresection

0, 60, Resection margin (RO rate) Tumor necrosis/infarction Significant increase in R0 rate in Significant increase in tumor the NBTXR3 arm necrosis/infarction in the NBTXR3 arm

*Statistically significant at an α of 5%; ITT FAS (Full Analysis Set) Source: Bonvalot et al, Lancet Oncol, 2019 NBTXR3 activated by radiotherapy (N=87) Radiotherapy alone (N=89) Safety – Phase II/III in STS Arm A Arm B NBTXR3 RT alone activated by RT (N=90) (N=89) • No change in Median Relative Radiation therapy dose intensity* Patients with any TEAE1 87 (97.8%) 87 (96.7%)

• No change in Median Duration of Patients with any NBTXR3 related TEAE 31 (34.8%) NA radiotherapy schedule (days) Patients with any TEAE leading to death (death 0 2 (2.2%) • No change in % of surgery performed regardless the causality assessment)

THE STUDY CONFIRMED: Patients with any serious TEAE 28 (31.5%) 14 (15.6%)

• Feasibility of injection Patients with any serious NBTXR3 related TEAE 9 (10.1%) NA Patients with any serious TEAE related to radiation • No change in dosage and schedule of current radiotherapy 5 (5.6%) 5 (5.6%) therapy standard of care Patients with any serious AE2 35 (39.3%) 27 (30.0%) • Good local tolerance (similar radiation safety in both arms) Patients withdrawn from study treatment due to TEAE 1 (1.1%) 0 • Manageable acute immunological reaction occurring at the

time of injection 1 Treatment Emergent AEs are AE observed during the on-treatment period. 2 Serious AEs are adverse events reported during the whole study period (i.e. on-treatment and follow-up periods). No impact on planned radiation and surgery. NA, not applicable

*Relative radiation therapy Dose Intensity = (Actual Dose Intensity / Planned Dose Intensity) Source: Bonvalot et al, Lancet Oncol, 2019

• A target population with high unmet needs: Frail and elderly patients that are ineligible to cisplatin and intolerant to cetuximab Main characteristics: low response rate, short PFS of ~7.3 months, short OS of ~12 months

• Positive Phase I escalation results: Well tolerated and promising efficacy (Best ORR = 69%) that could impact progression free survival, overall survival and quality of life

• Fast Track designation obtained in February 2020: FDA recognized the unmet need and the potential for NBTXR3 to fulfil that need

• New positive Phase I expansion results presented at ASCO (May 2020): Equivalent or even better efficacy (Best ORR = 83%) than escalation dose and well tolerated

Source: Claims data presented at MHNCS 2020; Amini et al. 2016, Bourhis et al. 2006 and Moye et al. 2015 • Stage III and IV • ≥65 years old and/or frail • Oral cavity, Oropharynx • HPV all status (positive & negative) • Ineligible for chemotherapy and intolerant to cetuximab in combination with RT

Source: Moye et al.,The Oncologist 2015 Dose escalation: 3 + 3 design to assess 4 dose levels** PRIMARY ENDPOINTS PATIENT POPULATION Dose escalation • ≥ 65 years-old 5% 10% 15% 22% • Assess DLTs, • KPS > 70 Recommended dose • Stage III or IVA HNSCC* of the oral (RP2D), MTD if possible cavity or oropharynx • Safety and tolerability Single intratumoral injection of NBTXR3 • Eligible for radiotherapy activated by Radiotherapy Dose expansion • Not eligible for cisplatin or cetuximab • Objective Response Rate • No metastases (ORR) and Complete Response Rate (CRR) of the • Adequate organ functions Dose expansion: 44 additional patients primary tumor, by imaging at the RP2D according to RECIST 1.1

* According to AJCC 7th edition for the dose escalation and 8th edition for the dose expansion ** Injected volume calculated as a % of tumor volume determined on an MRI performed <14 days prior to injection Amini et al. Bourhis et al. Moye et al. Literature data: 2016 2006 2015 NBTXR3 Phase I/II Study Population has a poor Overall Survival prognostic

Median OS at 12-13 months

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

Source: Amini et al., Cancer May 15, 2016; Bourhis et al., Journal of Clinical Oncology, June 2006; Moye et al.,The Oncologist 2015 AEs related to NBTXR3 injection Dose Level N DLT AE (n) SAE (n)

5% 3 No 0 0

10% 3 No 0 0

15% 5 No Grade 1 tumor hemorrhage (N=1) 0

Grade 2 oral pain (N=1) 22% 8 No Grade 1 asthenia (N+1) 0 Grade 1 injection site pain (N+1)

Recommended dose defined by DSMB as 22% 69 % Objective Response (incl. 56% complete response)

40 Progressive Disease

Dose Level 1-5% 20 Dose Level 2-10%

Dose Level 3-15% 0 Stable Disease Dose Level 4-22%

-20

-40

% change % baseline from Target Target lesion longest dimension

-60 Partial Response

-80

* * -100 * * Complete Response

Subtherapeutic dose • Head and Neck Newly Diagnosed and Treated (oral cavity • Head and Neck Newly Diagnosed and Treated (oral or oropharynx) cavity, oropharynx) • Elderly (65+) • Elderly (65+) • Stage III & IV • Stage III & IV • Ineligible for cisplatin • No cisplatin use during all treatment lines • Intolerant to cetuximab Median PFS: 7.3 months N=246

7,3

Note: PFS in RWE data is defined "as change in N or M staging", change of treatment" or "death". Change of treatment is usually correlated to relapse. A second line is therefore most often used in patients in this dataset. Study 102 patients • N=19

Claims data • PFS* • RT or RT + cetuximab • N=246

*PFS in RWE data is defined as «change in N or M staging », « change of treatment » or « death ». Change of treatment is usually correlated to relapse. A second line is therefore most often used in patients in this 7,3 dataset. All Treated Patients All Treated Patients Baseline Characteristics Baseline Characteristics N=40 N=40 Primary Tumor Stage1 Gender I2 1 (2.5%) Female 11 (27.5%) II2 5 (12.5%) Male 29 (72.5%) III 18 (45.0%) Age, years IV/IVA 16 (40.0%) Median 70.7 Karnofsky Score Min, Max 50.7, 89.9 100% 9 (22.5%) 3 Tumor Volume, mL 90% 10 (25.0%) Median 43.1 80% 15 (37.5%) Min, Max 1.3, 222.3 70% 5 (12.5%) Tumor Location Missing 1 (2.5%) Oral cavity 22 (55.0%) Hyper-polypharmacy Oropharynx 18 (45.0%) ≥8 ongoing medication 7 (17.5%) HPV status Comorbidities4 Missing 1 (2.5%) Cardiac disorder risk 28 (70,0%) HPV 16 + 11 (27.5%) Gastointestinal disorder risk 21 (52.5%) HPV 16 - 23 (57.5%) Weight loss risk 8 (20.0%) Not done 5 (12.5%)

1 According to AJCC 8th edition 2 Stage III/IV according to AJCC 7th edition 3 As per local imaging data. Abbreviations: HPV, human papilloma virus, OPC, oropharyngeal cancer 4 Most frequent Summary of AE/SAE AEs SAEs All Treated Patients N=40

All 404 (100%) 41 (10.1%)

Related to Injection procedure 13 (3.2%) 2 (0.5%)

Related to NBTXR3 18 (4.4%) 3 (0.7%)

Related to Radiotherapy 204 (50.5%) 19 (4.7%)

Note: AE/SAE incidence is calculated based on total number or AEs

No fatal Adverse Event related to NBTXR3 or the Injection Procedure 40 Progressive Disease

20

0 Stable

Disease (%)

dimension dimension -20 baseline longest * *

from -40 * * lesion

Partial change Response Target Target -60 Stable disease

Partial response

-80 Complete response

*Unconfirmed response -100 * * * * Complete Response N = 30 As of 30 April 2020

Evaluable Population for Objective Tumor Response has included all patients who have had at least 80% of the intended intratumoral dose of NBTXR3 and 60 Gy of IMRT and the required imaging for tumor burden evaluation (target lesions assessments), at baseline and at least once post treatment. Escalation (n=16)

Expansion (n=30) Tumor

Tumor NBTXR3

CT-scan 24h post IT injection CT-scan post radiotherapy CT-scan 7 months after RT A NBTXR3 + RT ± Cetuximab (250 pts) Endpoints Investigator’s choice • Primary: PFS R • Radiotherapy alone 1:1 • Secondary: OS, ORR, AEs, QoL B • Radiotherapy + Cetuximab RT (trial powered to demonstrate a significant ± Cetuximab (250 pts) difference on OS)

Readout: • Futility analysis: 18 months after first randomization • Interim analysis event-driven: 24-30 months; FDA advised that NBTXR3 could potentially qualify for accelerated approval • Final analysis on OS, PFS and quality of life

Hard to treat patient population: • Previous resection/local treatment is permitted • Hepatocellular carcinoma or Liver Mets • Unresectable/Medically Inoperable tumors • ECOG 0 or 1 PATIENT POPULATION 3 + 3 Design to assess 5 dose levels ENDPOINTS • ≥ 18 years-old 10% 15% 22% 33% 42% • ECOG 0 or 1 • Assess DLTs, RP2D, MTD • Hepatocellular Carcinoma • Safety and tolerability (HCC) patients Injected volume calculated as a % of tumor – Unsuitable for surgery or local volume determined on an MRI performed • Liver function: Child-Pugh score treatment <14 days prior to injection (ALBI also explored) – Child Pugh A–57 • – With or without portal vein thrombosis Early signs of anti-tumor activity per mRECIST (HCC) / RECIST 1.1 – Life expectancy > 3 months Single intratumoral injection of NBTXR3 (Mets) • Liver metastases (Mets) patients activated by radiotheraoy – Unresectable tumor(s) – Life expectancy > 6 months

Cf Clinicaltrial.gov Dose Evaluable Patients Complete Response Partial Response Level n n, (%) n, (%)

ALL 8 5 (62.5) 3 (37.5)

Patients were recruited at different time points during the trial; those receiving the highest doses are thus the ones with the lowest follow-up. 4 cm 45-50 Gy @ NBTXR3 Prospective SBRT 11 90/10/0 - 100% 1yr 100%* (1.1-5.4) 10-15 Gy/fx *On evaluable patients NBTXR3 dose Preferred term Worse grade AE (n) SAE (n)

10% Malaise Grade 2 1 0

15% Abdominal pain Grade 3 2 0

Bilateral pleural Grade 1 1 0 effusion 22%

Bile duct stenosis Grade 3 1 1

33% Fatigue Grade 1 1 0

No NBTXR3 related DLT / No leakage in surrounding tissue

Hot

Cold

Hot CD8

Cold No infiltration Limited infiltration Massive infiltration of immune cell of immune cell of immune cell Adapted from Alexandrov et al. (2013) and Gentles et al. (2015) Nivolumab: Checkmate 141 Recurrent Head and Neck

Non-responder

Responder

Source: Ferris et al, NEJM, 2016 Checkpoint inhibitors refractory patients in NSCLC and H&N

Nivolumab: Checkmate 141 Recurrent Head and Neck

Goal: Transform the non- Non-responder responders into responders with NBTXR3 and RTx

Responder COHORT 1: Anti-PD-1 non-responders (pembrolizumab or Locoregionally recurrent AND metastatic nivolumab): HNSCC • SD for at least 12 weeks or confirmed PD at 8 – 12 weeks after immunotherapy treatment

COHORT 2: Patients with lung metastasis Any primary tumor eligible for anti-PD-1

COHORT 3: Patients with liver metastasis Any primary tumor eligible for anti-PD-1 RTx + NBTXR3 Biopsy Baseline Pre Treatment Tumor Tissue Post Treatment

RTx Alone Phase III Soft Tissue Sarcoma Biopsy Baseline Pre Treatment Tumor Tissue Post Treatment biomarker data

PD-1 log2 ≥1 log2 ≥1 6/26 (23%) 11/23 (48%) log2 ≥1 log2 ≥1 9/26 (35%) 9/22 (41%)

log2 ≤1 log2 ≤1 8/26 (31%) 4/23 (17%) log2 ≤1 log2 ≤1 11/26 (42%) 5/22 (23%)

Source: Immunorad 2018, Paris, France

H&N Expanding across oncology Phase II Trial of reirradiation with NBTXR3 combined with anti-PD-1/L1 for inoperable, locally advanced H&N cancer with MD Anderson: H&N 9 clinical trials planned Phase II Trial for NBTXR3 for recurrent/metastatic HNSCC patients with limited PD-L1 expression • Clinical collaboration will initially support nine (9) Lung phase clinical trials Phase II Trial for NBTXR3 combined with anti-PD-1 or anti-PD-L1 in Stage • Multiple indications: Head & Neck, Pancreatic, IV lung cancer Esophagus, Lung Lung • Involving approximately 340 patients Phase I Trial for NBTXR3 in lung cancer patients in need of reirradiation • Risk sharing funding scheme: Backloaded payment & post FDA registration payment Advanced Tumors/Lung/Liver Phase I Trial for NBTXR3 combined with anti-CTLA4 and anti-PD-1 or PD- L1 in patients with advanced solid tumors and lung or liver mets Pancreas Phase I Trial for NBTXR3 in pancreatic cancer

Esophagus Phase I Trial for NBTXR3 in esophageal cancer patients

Two additional trials under discussion

• NBTXR3 is a radioenhancer with the potential to improve outcomes for millions of oncology patients • Disruptive technology with universal, physical MOA • Eight (8) ongoing clinical trials (H&N, lung, liver, pancreas, prostate, etc.) and an additional 7 contemplated

• Clinical proof of concept established in a randomized Phase III trial in STS (featured in The Lancet Oncology) • First European market approval (CE Marking) obtained • IP (300+ patents issued or in process of issuance) • Positive PI in H&N and Liver showing strong potential for improving survival and quality of life, well tolerated

• Phase III in locally advanced H&N registration in US to begin • I/O combination trial results in PD-1 resistant patients in recurrent H&N • European expansion Phase I end of recruitment in locally advanced H&N

• Publicly-traded, Euronext : NANO – ISIN : FR0011341205 • Cash: EUR 26.6M as at June 30, 2020 + EUR 5M of State-Guaranteed Loan and EUR 20M of private placement, > 12 months cash visibility • Completion of Phase I expansion in H&N by end of 2020. • Update on efficacy and safety in Phase I expansion in H&N cancer by Q4 2020. • First data in IO trial to be reported in medical congresses by Q4 2020. • Preclinical data in I/O by MDA expected at AACR. To be presented later in 2020 at first possible congress.

• Phase I/II in H&N cancer with PE (w/ chemo): recruitment completion by end of 2020. • Phase I/II in rectum cancer with PE (w/ chemo): recruitment completion by end of 2020. • MDA trials: Pancreas trial to launch; first patient expected to be injected in by Q3 2020. • MDA trials: Moving through regulatory process in several indications, FPI to be defined post-COVID-19.

• Phase I in Liver cancer: follow up to be presented by the end of the year. • Post-approval trial in STS: trials authorization postponed to Q2 2021 due to COVID-19.

* Timelines are subject to changes depending on the COVID-19 situation 6 months to June 30 FINANCIALS in K€ 2020 2019 Total revenue and other income 1,448 1,823 Share capital breakdown (as of August 2020) based on Operating revenues 37 37 26,031,122 shares Other income 1,411 1,786

Research & Development (R&D) expenses (13,077) (13,380) Selling, General and Administrative (SG&A) costs (6,755) (8,910) Total operating expenses (19,832) (22,290) 42% Institutional investors Operating income (18,384) (20,467) Family offices 50% Financial income 234 724 Management and employees Financial expenses (2,428) (4,176) Retail

Net financial income (2,194) (3,452) Income tax (1) - 3% 5% Net loss for the period (20,579) (23,920)

Cash availability as at June 30, 2020 amounted to €26.6M [email protected]