Scientific Clinical | NANOBIOTIX: new translational data presented at ASTRO, NCI AND SITC’S Immunotherapy Workshop

• Translational data showing tumor immune activity and positive Tumor Infiltrating Lymphocytes (TILs) in human and mouse model
• Confirmation of the ability to transform "cold" tumors into "hot" tumors and that NBTXR3 treatment may have an impact on the tumor microenvironment
• Opening up of the potential for NBTXR3 to treat metastases

Paris, France and Cambridge, Massachusetts (USA), June 15, 2017 - NANOBIOTIX (Euronext: NANO - ISIN: FR0011341205), a late clinical-stage nanomedicine company pioneering new approaches to the treatment of cancer, today presented new translational data at the "Immunotherapy workshop - Incorporating Radiation Oncology into Immunotherapy" co-sponsored by the American Society of Radiation Oncology (ASTRO), the National Cancer Institute (NCI) and the Society for Immunotherapy of Cancer (SITC), that takes place from June 15 to 16, 2017 in Bethesda, Maryland, USA.

Nanobiotix's lead product, NBTXR3, has a universal physical mode of action which is designed for the local destruction of tumors. In addition to the physical destruction of cancer cells, recently published data suggests that NBTXR3 generates immunogenic cell death which could trigger a specific immune response to attack the tumor.

Many tumors exhibit little or no response to therapies targeting the immune system and are considered "cold". The explanation for the lack of response in its simplest form, is a lack of immunogenicity. The ability of NBTXR3 to generate intratumoral immunogenic cell death (ICD) could be a key to significantly increasing the number of patients who can benefit from the help of their immune system to fight their cancer.

Today, Nanobiotix presented new translational data from its immuno-oncology program.

"Hafnium oxide nanoparticle, a potent radiation enhancer for in situ cancer vaccine" (June 15, 2017)

1. Galon1, M. Laé2, Z. Papai3, P. Rochaix4, L.C. Mangel5, F. Hermitte6, Z. Sapi7, M. Delannes4, T. Tornoczky5 , A. Vincent- Salomon2, V. Servois2, H. Brisse2, S. Paris8, A. Pottier8, and S. Bonvalot2

   1INSERM, Paris, France, 2Institut Curie, Paris, France, 3Magyar Honvedseg Egeszsegugyi Kozpont, Budapest, Hungary, 4Institut Universitaire du Cancer, Toulouse, France, 5Pecs University, Pecs, Hungary, 6HalioDx, Marseille, France, 7Semmelweis University, Budapest, Hungary, 8Nanobiotix, Paris, France.

2. Human Soft Tissue Sarcoma (STS) patients data

   In tumors of STS patients, a significant increase of T cells (CD3+, CD8+) and a marked increase of dendritic cell (CD103+) infiltrates in post- versus pre-treatment were observed for NBTXR3 plus radiotherapy arm, while no differences were seen in the use of radiotherapy alone. These findings demonstrate the ability of NBTXR3 to transform cold tumors (as Soft Tissue Sarcoma) in hot tumors.

   Large hemorrhagic zones have been found in tumor tissues treated with NBTXR3, whereas tumors treated with radiotherapy alone did not show such patterns. This finding shows that NBTXR3 could affect the tumor microenvironment and potentially allow better infiltration of activated T Cells.

   The upregulation of adaptive immunity gene expression between pre- and post-treatment was pronounced for NBTXR3 plus radiotherapy - 72 genes only up-regulated with the NBTXR3 treatment, showing enrichment of cytokine activity and of the T cell receptor signaling pathway.

   A number of upregulated genes correspond to existing or promising IO targets, enabling a potential combination of NBTXR3 with therapeutic approaches, like products targeting PD1, PDL1, CTLA4, etc. This data requires confirmation in additional studies.

   Asymmetrical volcano plot shows a trend toward the upregulation of panimmune genes in post-treated tumors of Soft Tissue Sarcoma patients. The two charts compare the results of patients treated with radiotherapy alone (left), with patients treated with radiotherapy plus NBTXR3 (right).

3. Mice model (CT26) data

   In mice, the abscopal effect (i.e. an effect outside the scope of the localized treatment) was evaluated. A tumor was implanted on each side of each mouse; one of the tumors was treated with either NBTXR3 and radiotherapy, or radiotherapy alone; while the other remained untreated. The treated tumors, both those that received NBTXR3 and radiotherapy and those that received radiotherapy alone, demonstrated volume shrinkage.

   However, the study showed that only the use of NBTXR3 with radiotherapy resulted in a control on the untreated tumors (abscopal effect). No effect was observed in control groups and groups treated with radiation therapy alone.

   In this model, NBTXR3 plus radiotherapy induces a noticeable increase of CD8+ and macrophages infiltrates in both tumors (treated and untreated). At the same time, no effect was observed in cases where radiotherapy was used alone, when compared to control groups (that received no irradiation). This demonstrates that NBTXR3 plus radiotherapy can induce a marked systemic antitumor immune response on distant and untreated tumors where radiotherapy alone couldn't.

4. Conclusion

5. Taken together, these non-clinical and preliminary clinical results confirm that NBTXR3 plus radiotherapy could efficiently prime the adaptive antitumor immune response, turning "cold" tumors in "hot" tumors. Additionally, these results suggest that the physically-induced response and subsequent immune activation triggered by the NBTXR3 treatment could be generic. NBTXR3 with radiotherapy could transform these tumors into an effective in situ vaccine, opening up very promising perspectives in the treatment of local cancer and metastases.

   Tumor Immune Cell Infiltrates (TILs)

   NBTXR3 competitive positioning in IO

   Many IO combination strategies focus on 'priming' the tumor, which is now becoming a prerequisite of turning a "cold" tumor into a "hot" tumor.

   Compared to other modalities that could be used for priming the tumor, NBTXR3 could have a number of advantages: The physical and universal mode of action that could be widely applied across oncology; the one- time local injection and good fit within existing medical practice already used as a basis for cancer treatment, as well as a very good chronic safety profile and well-established manufacturing process.

   The new clinical data and previous pre-clinical data indicate that NBTXR3 could play a key role in oncology and could become a backbone in immuno-oncology.

   ***

   About NANOBIOTIX: www.nanobiotix.com

   Nanobiotix (Euronext: NANO / ISIN: FR0011341205) is a late clinical-stage nanomedicine company pioneering novel approaches for the treatment of cancer. The Company's first-in-class, proprietary technology, NanoXray, enhances radiotherapy energy with a view to provide a new, more efficient treatment for cancer patients.

   NanoXray products are compatible with current radiotherapy treatments and are meant to treat potentially a wide variety of solid tumors including soft tissue sarcoma, head and neck cancers, liver cancers, prostate cancer, breast cancer, glioblastoma, etc., via multiple routes of administration.

   NBTXR3 is being evaluated in: soft tissue sarcoma (STS), head and neck cancers, prostate cancer, and liver cancers (primary and metastases). Additionally, head and neck cancer and rectal cancer trials led by Nanobiotix's Taiwanese partner, PharmaEngine, are underway in the Asia Pacific region. The Company has filed in August 2016 for market approval (CE Marking) in Europe for its lead product NBTXR3.

   The Company started in 2016 a new preclinical research program in Immuno-oncology with its lead product NBTXR3, which could have the potential to bring a new dimension to cancer immunotherapies.

   Nanobiotix is listed on the regulated market of Euronext in Paris (ISIN: FR0011341205, Euronext ticker: NANO, Bloomberg: NANO: FP). The Company Headquarter is based in Paris, France. Affiliate in Cambridge, United States.

   Contact

   Nanobiotix
   Sarah Gaubert Director, Communications & Public Affairs +33 (0)1 40 26 07 55 sarah.gaubert@nanobiotix.com / contact@nanobiotix.com	Noël Kurdi Director, Investor Relations +1 (646) 241-4400 noel.kurdi@nanobiotix.com / investors@nanobiotix.com
   Media relations
   France - Springbok Consultants Marina Rosoff +33 (0)6 71 58 00 34 marina@springbok.fr	United States - RooneyPartners Marion Janic +1 (212) 223-4017 mjanic@rooneyco.com

   Disclaimer

   This press release contains certain forward-looking statements concerning Nanobiotix and its business. Such forward-looking statements are based on assumptions that Nanobiotix considers to be reasonable. However, there can be no assurance that the estimates contained in such forward-looking statements will be verified, which estimates are subject to numerous risks including the risks set forth in the update of the reference document of Nanobiotix filed with the French Financial Markets Authority (Autorité des Marchés Financiers) under number D.16-0732-A01 on December 27, 2016 (a copy of which is available on www.nanobiotix.com) and to the development of economic conditions, financial markets and the markets in which Nanobiotix operates. The forward-looking statements contained in this press release are also subject to risks not yet known to Nanobiotix or not currently considered material by Nanobiotix. The occurrence of all or part of such risks could cause actual results, financial conditions, performance or achievements of Nanobiotix to be materially different from such forward-looking statements.

   This press release and the information that it contains do not constitute an offer to sell or subscribe for, or a solicitation of an offer to purchase or subscribe for, Nanobiotix shares in any country. At the moment NBTXR3 does not bear a CE mark and is not permitted to be placed on the market or put into service until NBTXR3 has obtained a CE mark.