Disclaimer Presentation NBTX_ENF June 2013

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1 ENF 2013

2 Disclaimer Receipt of this presentation implies your agreement with the restrictions outlined below. This presentation does not constitute or form part of, and should not be construed as, an offer of securities for sale or an invitation or inducement to invest in securities in France, the United States or any other jurisdiction. Securities may not be offered or sold in the United States absent registration or an exemption from registration. No public offering of securities will be conducted in France or abroad prior to the delivery by the French Autorité des marchés financiers (Financial Markets Authority) of a visa on a prospectus that complies with the provisions of Directive 2003/71/CE. No public offering of securities is contemplated in France or any jurisdiction outside France. This presentation includes only summary information and does not purport to be comprehensive. Certain information included in this presentation are not historical facts but are forward-looking statements. The forward-looking statements are based on current beliefs, expectations and assumptions, including, without limitation, assumptions regarding present and future business strategies and the distribution environment in which Nanobiotix operates, and involve known and unknown risk, uncertainties and other factors, which may cause actual results, performance or achievements, or industry results or other events, to be materially different from those expressed or implied by these forward-looking statements. Forward-looking statements speak only as of the date of this presentation and are for illustrative purposes only. Forward-looking information and statements are not guarantees of future performances and are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Nanobiotix, that could cause actual results to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. 2

3 Today s Speakers Pioneer in nanomedicine 20 years in nanobusiness Leading roles in several nanomedicine-organizations Vice President European Technology Platform nanomedicine, Laurent Levy CEO and Co-founder Expert for Euro-nanomed funding agency and French ministry of research) Phd in physical chemistry, specialized in nanotechnology from the Pierre and Marie Curie University (Paris) and from the CEA (Commissariat à l Énergie Atomique et aux Énergies Alternatives) and a DEA (advanced studies and diplomas) in physics of condensed matter from the UPVI-ESPCI (Paris) 3

4 The nano revolution in medicine Macroscopic approach Object manufactured to provide function MRI, Scanner, scalpel, artificial heart, syringes Molecular domain Molecules to interact at sub-cellular level Drugs, Biologics, NANO approach Manufactured objects with tunable functions that can interact at sub-cellular level Only nanomedicine allows the design of object that could deliver physical mode of action ( functions) at the sub cellular level 4

5 NANOBIOTIX: Nano therapy for mega markets A nano technology......revolutionizing therapy in oncology with meaningful solutions The potential of a blockbuster with fast track to market A unique business model with limited risk compared to drug development The Nanotech Revolution in Oncology 5

6 NANOBIOTIX at a glance Founded in 2003 Pioneer in nanomedicine developing a pipeline of first-in-class products targeting cancer Traded on Euronext Paris (NANO / ISIN: FR ) A first industrial partner for development and commercialization of first product in Asia ($57M total value, UF and Milestones) NBTXR3, first product, achieves clinical milestone reaching Proof-Of-Concept in Phase I Trial of Soft Tissue Sarcoma Cash raised to date 40m (including 14M at IPO Q4 2012) Cash position as of Dec, 2012 : 12,4m cash equivalent 33 employees 6

7 Revolutionizing local treatment in oncology

8 NANOBIOTIX targets an unmet medical need shared by millions of patients Radiotherapy is one of the major local treatments for cancer 60%* of cancer patients (6M) receive radiotherapy Radiotherapy can destroy any tumor cell if the right dose is applied Radiotherapy is one of the key treatment tools for cancer but has limitations Source: * RADIATION THERAPY EQUIPMENT A global strategic business report 08/06 8

9 Radiotherapy damages healthy tissues Overview of Xray s distribution in water Tumor Xray track Energy deposition 50 cm 20 cm 20 cm MeV Xray beam damage healthy tissue when targeting the tumor Source: Geant 4 modelisation 9

10 The key question Healthy tissues Tumor Healthy tissues How to improve the energy dose within the tumor without increasing the dose in healthy tissues? To maximize efficacy and bring benefit in different clinical situations: Adjuvant, Neo-adjuvant, Definitive treatment, Palliative therapy Source: * RADIATION THERAPY EQUIPMENT A global strategic business report 08/06 10

11 Nanoparticles Antibody Virus Bacteria Cancer cell 50nm nanometer Nanoparticles domain 1 nm = 10-9 m hair 100,000 nm Only nanoparticles are small enough to move into cells 11

12 Nanoparticles maximize Xray absorption in the tumor NanoXray Technology Beside the size, Nanoparticles should exhibit 2 key features 1)Absorb Xray 2)Non-toxic material 50 nanometer HfO 2 * particles where chosen because they have the best ratio for Xray absorption and non toxicity NanoXray acts as a true radioenhancer with a physical mode of action Note: *HfO2: Hafnium Oxide 12

13 Increase the dose within the tumor without increasing the dose in healthy tissues Dose Radiotherapy alone Dose Radiotherapy with NANOXRAY Radiotherapy dose in the cell Plus 9 fold Dose* around nanoparticles Standard dose d Standard dose d Cell 2 µm NanoXray increases the radiotherapy dose in the cell by 9 folds 2 µm Clusters of Nanoparticles (few 100s) Note: Dose enhancement determined by montecarlo simulation (CEA Saclay, France) 13

14 NanoXray Absorbs the energy in the tumor Increased dose in the tumor Standard dose X ray Tumor Healthy tissues NanoXray increases the radiotherapy dose in the tumor without increasing the dose/damage to healthy tissues 14

15 A solid pipeline to cover most of radiotherapy applications Pipeline based on the same HfO 2 nanoparticles with different coatings to address the needs of different clinical situations: PERSONALIZED THERAPY INTRA TUMORAL INJECTION where access is appropiate POST SURGERY RADIOTHERAPY Gel for Tumor bed deposition during surgery INTRA VENOUS INJECTION tumor or organ anatomy access, staging Local administration to optimally improve the therapeutic index by delivering the product where needed only Systemic administration when local one is not appropriate (tumor / patients specific characteristics) 15

16 An unmet medical need shared by many patients all over the world Target patient population in USA, Japan and EU 5 for initial indications of the portfolio Indication Incidence Target patient population Soft Tissue Sarcoma 23,030 11,795 Esophageal Cancer (neo-adjuvant and definitive) Indications with high unmet need NBTXR3 32,556 22,789 Rectal Cancer 94,823 75,858 Hepatocellular Carcinoma 97,113 46,614 Head and Neck Cancer (subset population) 137,048 13,705 Advanced Prostate Cancer 418,000 62,700 Glioblastoma 47,202 22,759 Total 849, ,220 Indication Incidence Target patient population Breast Cancer 447, ,896 Prostate Cancer 418, ,646 Non-Small Cell Lung Cancer 413, ,907 Vertebrae Metastases 227,816 70,623 Brain Metastases 114,824 57,412 Advanced Head & Neck Cancer Largest target Indications NBTX-IV & NBTX-TOPO 137,048 41,114 Cervical Cancer 42,090 16,836 Total 1, ,034 Incidence and target population ( 1): US, Japan, Top 5 EU markets Ref Datamonitor ref. DMHC2593, DMHC 2467, DMHC 2339 and DMHC 2319 ; ref. HC , HC and HC million patients in 7 countries leading to 2 million taking into account fast growing markets like China, Russia, Brazil, India 16

17 clinical development with fast time to market

18 Strategy to create value rapidly and efficiently NBTXR3 Development in Europe up to market (Medical device) Rapid route to market to generate recurrent revenue In house clinical development up to market In Asia, partnership with PharmaEngine Short term revenue, milestones and royalties Create value through data (that can be used in EU) And in USA, partnership Medium term revenue, milestones and royalties. US market access Other products (IV and TOPO) Revenues generated will be invested in other products to create value Clinical development to market in the EU, established partnership in Asia Pacific for the first product, partnership to be sought in the US 18

19 NBTXR3, STS trial: Clinical Proof Of Concept Communication in Chicago on June, 1 st 2013 : Radiotherapy + NBTXR3 Tumor NBTXR3 19

20 NBTXR3: Clinical development plan Soft Tissue Sarcoma pilot trial as an ideal start of clinical development Expending uses of the product through different indications Head and Neck cancer in Europe 3 indications funded and developed by PharmaEngine in Asia-Pacific Nanobiotix (Europe) Soft Tissue Sarcoma Head & Neck 3rd indication TBD PharmaEngine (Asia) Rectal Cancer Liver or Esophagel Liver or Esophagel Pilot Study (20 40 pts) Pivotal Study ( pts) Regulatory Approval Estimated planning Ongoing trials Low investment and balanced risk for a broad development in Europe and in Asia Pacific Note: indicative development plan of PharmaEngine 20

21 News flow Launch of H&N clinical trial in Europe for NBTXR3 New clinical results on STS achieving NBTXR3 Proof of Concept IPO on Nyse-Euronext oversubscribe x2 57M deal with PharmaEngine on NBTXR3 in Asia Launch of clinical development in Asia (PE) for NBTXR3 Completion of STS Phase I/II Lead validation of pipeline second product New industrial partnership Intermediate results on new indications for NBTXR3 in Asia and Europe Lead validation of pipeline third product 21

22 Contact Laurent Levy CEO

23 NBTXR3: Pilot study Soft tissue sarcoma An open-label, single arm, feasibility and safety phase I study with NBTXR3 intra tumor implantation (by injection) and activated by external beam radiation therapy in patients with soft tissue sarcoma of the extremity Study Center: Institut Gustave Roussy, France (Dr Eric Deutsch, Dr Sylvie Bonvalot) 27 patients; 4 steps dose escalation study (injection of a growing volume of NBTXR3 in comparison to total tumor volume) Primary Objectives Feasibility of NBTXR3 intra tumoral implantation Safety and determination of an early dose limiting toxicity (DLT) of NBTXR3 intra tumoral implantation (if any) Secondary Objectives Anti-tumor activity of NBTXR3 in terms of pathological Response (pr), Response Rate (RR) as per RECIST, Amputation rate, Body kinetic profile of NBTXR3 radiation therapy Proof Of Concept announced in June 2013: 12 patients already treated with positive outcomes Source: 23

24 The oncology revolution with nanomedicine Molecules (drugs and biologics) Nanotechnology supports the effect of molecules Nano-object becomes the active principle 1940 s 1980 s 2000 Today Chemistry Biology Nanosized drug delivery system New therapeutic tools based on physics e.g. Mechlorethamine e.g. Herceptin e.g. Doxil e.g. NanoXRay Physics Biology 24

25 A proprietary technology, with established GMP manufacturing 6 patent families protecting the entire concept and products Freedom to operate Manufactured in a qualified and validated GMP process Price for manufacturing within the standard of chemical product Strong IP protection and market exclusivity until 2029 minimum Robust and affordable process for manufacturing 25

26 A first partnership with PharmaEngine on NBTXR3 for Asia-Pacific area Accelerate the value creation through partnership without giving the all potential Small part of the value shared through this partnership establishing minimum target upside Validation of the technology approach by a leading oncology development company in Asia A partnership that will allow parallel development of NBTXR3 in EU and Asia increasing value and reducing time to market for larger number of indications Asia Plan Minimum of three phases I and two phases II (Pivotal). Revenues 1M$ upfront payment in 2012 and milestones payments of up to 56M$ Eligible for double digit royalties Presentation NBTX ENF june

27 Focused and Experienced management Lean company with highly experienced team covering all aspects of pharmaceutical and medtech development Laurent Levy, CEO and Co-founder Pioneer in nanomedicine, 20 years in nanobusiness Leading roles in several nano-organizations (e.g. VP, ETP nanomedicine, Euro-nanomed funding agency and French ministry of research) Elsa Borghi, CMO Successfully involved in clinical trials and registrations of several oncology drugs at Sanofi-Aventis Philippe Mauberna, CFO Broad Financial experience in the Life Sciences Industry with successful EMEA operational project management in Financial Effectiveness Bernd Mühlenweg, CBO Track record in partnering, licensing and M&A Formerly with WILEX AG Maija Hietava-Lorenzi, Head of Q&A CMC Broad experience in CMC as Qualified Person and as an international inspector Formerly with World Health Organization, Ark Therapeutics, Fit Biotech Plc and Finnish Medicines Agency Agnès Pottier, Head of Discovery Expert in synthesis of nanomaterials R&D leadership roles for more than a decade Formerly with Rodhia 27

28 NanoXray Absorbs the energy in the tumor Maximal Dose Tolerated Maximal Dose Tolerated 1 Cure Adverse event Therapeutic window 1 Cure Adverse event Therapeutic window Probability RT dose (Gy) standard radiotherapy Probability RT dose (Gy) with NanoXray NanoXray increases the radiotherapy dose in the tumor without increasing the damage to healthy tissues 28

29 Clear focused pathway to revenues with a large upside Europe Asia US NBTXR3 Intra tumoral Integrated development 150,000 patients Partnership with PharmaEngine 520,000 patients Partnership (est. 2014) 150,000 patients Expediting route to market and maximizing commercial opportunity NBTX IV Intra venous 174,000 patients 330,000 patients 4 170,000 patients NBTX TOPO Post surgery 246,000 patients 265,000 patients 262,000 patients Capitalizing on Development and commercialization expertise Ongoing plan to create value targeting more than 600,000 patients with a large upside potential on the other Products/areas Notes: Numbers are company estimation and taking into account more than the top 7 countries (e.g. China, India, Russia) 29

30 A 50 year old obstacle Radiotherapy must increase its efficacy Maximum tolerated dose 1 Cure Adverse event Therapeutic window Probability 0.5 Even a 5% to 20% increase of the therapeutic window could drastically change clinical output. Radiation oncologist, France RT dose (Gy) Solve the biggest limitation of RT: How to increase dose in the tumor without increasing dose in the healthy tissue? 30

31 A nanomedicine perfectly integrated in the existing care processes First assessment Diagnostic workup single Injection Before the first session of Radiotherapy Rx Decision Making Radiotherapy Treatment Follow up Review Consultation Complementary to the existing standard of use in oncology Low attrition risk due to a proven mode of action routinely used in hospitals Disruptive in its outcome, non disruptive in its mode of action No change in medical practice: patient flow will be minimally impacted as only one injection is added before first radiotherapy session 31

32 Several billions $ market potential for initial indications Forecast sales of the top 20 cancer therapy brands in the seven major markets ($m) Price examples for oncology treatments: Temodar 10-20k USD per year Avastin 100k USD per year > patients > patients > patients NanoXray are oncology products that could target more than 1, 000,000 patients in the seven major market Sources: Datamonitor Market and Product Forecasts: Top 20 Oncology Therapy Brands oct

33 Limitations of competitors Biological uncertainties Radioactive material Collateral damages on healthy tissues New RT equipment IMRT, IGRT, SBRT NA Brachytherapy and Radioimmunotherapy Biological approach Radioprotectors, radiosensitizers NA NanoXray NA Source : Référence : grouph, Evaluation Commerciale du portefeuille NanoXray, Janvier 2010 NanoXray is the only approach having all requirements to solve radiotherapy needs and could be used in synergy with all other improvements 33

34 NBTXR3: Safety & Toxicology Summary NBTX3 is safe and well tolerated in all preclinical studies NBTXR3 evaluated in most sensitive models for toxicity exploration: mice, rats, rabbits Fulfilling ISO and injectable product regulations requirements No major toxicities, and the immune system is not affected by administration of NBTXR3 Authorization for clinical trial given by ANSM A unique safety profile in oncology: 1 Offering a potential low risk for patients 2 Making it compatible with others therapies 34

35 NBTXR3: Intra tumoral injection and distribution Cat soft tissue sarcoma trial (n= 6 cats) Single intra tumoral injection (35% of tumor volume at baseline), no irradiation Bone Bone tumor Feasibility of intra tumoral administration and good tumoral dispersion of NBTXR3 with no leakage in surounding healthy tissues 35

36 NBTXR3: Antitumor efficacy in animal models Response translates into a significant difference HCT 116 (radiosensitive) colorectal cancer xenograft model Human colon cancer cell line. Swiss nude mice (8 per group) Single intra tumoral injection followed by two doses of radiation (first fraction 24h after IT injection) TV(mm3) NBTXR3 inj Fraction 4Gy (+1 day) Fraction 4Gy (+ 2 days) Days NBTXR3 creates a huge difference in tumor response after only 2 fractions of radiotherapy (2x 4 Gy) 36

37 NBTXR3: Antitumor efficacy in animal models Response translates into survival HCT 116 (radiosensitive) colorectal cancer xenograft model Percent survival Radiotherapy + NBTXR3 Radiotherapy alone Vehicle Vehicle+RT (2X4Gy) Vehicle+RT (1X8Gy) NBTXR3 NBTXR3+RT (2X4Gy) NBTXR3+RT(1X8Gy) Days translating into prolonged survival 37

38 NanoXray application Maximal Dose Tolerated Maximal Dose Tolerated 1 Cure Adverse event Therapeutic window 1 Cure Adverse event Therapeutic window Probability RT dose (Gy) standard radiotherapy Probability RT dose (Gy) with NanoXray NanoXray increases the radiotherapy dose in the tumor without increasing the damage to healthy tissues

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