Soft Tissue Sarcoma Results. June 2018

Transcription

1 Soft Tissue Sarcoma Results June 2018

2 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. This document has been prepared by Nanobiotix SA (together with its subsidiaries, the Group ) and is for information purposes only. The content of this document is provisional and for information purposes only and is not to be construed as providing investment advice. The information, statements and opinions contained in this document (the Information ) are provided as of the date of this document only and may be subject to significant changes at any time without notice. Neither the Group, nor its advisors, 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 makes no 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 verification and 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 to companies 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) under number D on April 28, 2017, in any other periodic report and in any other press release, which are available free of charge on the websites of the Group ( and/or the AMF ( This document contains 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 been obtained 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's own 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 where such 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. No public offering of securities 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 as amended. This document is for information purposes only and does not constitute an offering document or an offer of securities to the public in the Unite d Kingdom to which section 85 of the Financial Services and Markets Act 2000 of the United Kingdom applies. Securities may not be offered or sold in the United States absent registration under the US Securities Act of 1933, as amended, or an exemption from registration thereunder. This document contains certain forward-looking statements. All statements in this document 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, marketing strategy regulatory calendar, clinical milestones, assumptions and hypothesis, clinical development approach and financial requirements and are based on analyses of earnings forecasts and estimates of amounts not yet determinable and other financial and non-financial information. Forward-looking statements are subject to a variety of risks 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 any circumstance, be construed as a guarantee of the Group's future performance as to strategic, regulatory, fi nancial or other matters, and the Group s actual performance, including its financial position, 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 contained in this document. 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 the forward-looking statements contained in this document, such results or developments cannot be construed as a reliable indication of the Group's future results or developments. The Group expressly 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 or circumstance that may occur after the date of this document. 2

3 NANOBIOTIX ANNOUNCES POSITIVE PHASE II/III TOPLINE DATA IN SOFT TISSUE SARCOMA WITH NBTXR3 The trial achieved its primary endpoint of pathological Complete Response Rate (pcrr) The trial achieved its secondary endpoint in operability (R0 rate) NBTXR3 demonstrates significant superiority and clinical benefits for patients versus standard of care Safety profile confirmed This randomized trial validates the first in class mode of action of NBTXR3 3

4 One of the largest oncology markets with large unmet medical need Cancer patients 60% RTx More than 60% of all cancer patients receive Radiation Therapy Unmet medical need improve local control of tumor reduce relapse rate improve metastatic patient outcome More than 9 million / year Source: * World Health Organization (2014); **RADIATION THERAPY EQUIPMENT A global strategic business report 08/06 4

5 Nanobiotix targets radiation therapy - one of the largest oncology markets with minimal competition Conventional radiation therapy Around 60%* of cancer patients receive radiotherapy as a local treatment TUMOR Destroys any cancer cell at the right dose 50 cm Important limitations due to toxicity on healthy tissues 20 cm 100 photons at 6 MEV MeV Energy deposition 20 cm Xray track How to improve the energy dose within the tumor without damaging healthy tissues? Source: * RADIATION THERAPY EQUIPMENT A global strategic business report 08/2006 5

6 Solution: NBTXR3 maximizes Xray absorption in the tumor Technology key features: 1 Nanosized to enter cell 50nm 2 Designed to strongly absorb Xrays 3 Designed to be non-toxic HfO2 nanoparticles; electron microscopy picture 50 nanometer HfO 2 * particles were chosen because they have the best ratio for X-ray absorption and non-toxicity IP: concept and products protected by 10 patent families until at least 2029 * HfO2: Hafnium Oxide Source: Maggiorella et al. (2012) 6

7 NBTXR3 has a physical mode of action: Increase dose absorption & deposition in the tumor Radiotherapy Radiotherapy with NBTXR3 9X Dose* around nanoparticles *Note: Dose enhancement determined by montecarlo simulation (CEA Saclay, France) 7

8 NBTXR3 universal MOA triggering cellular destruction and adaptative immune response NBTXR3 +RTx large energy deposition in a nano-volume physical damage Clustered Nanoparticles in cytoplasm Dendritic cell activation Structural Damage DNA damage Stress Immunogenic Cell Death Sting pathway activation CD4 & CD8 activation Tumor Infiltration and Cell Killing Direct Cell Death (Apoptosis, Necrosis, ) 8

9 NBTXR3 First in Class Radioenhancer Physical Mode of Action that could work across all solid tumors Only one administration Fits into existing standard of care No change in equipment No change in current patient flow No change in protocol One product fitting in current practice helping millions of patients every year 9

10 NBTXR3 already used in clinical trials across EU, US and Asia 74 clinical centers using NBTXR3 Advanced development / pre-commercialization STS, H&N, Prostate, Rectum, NSCLC, HCC, Liver Mets 7 clinical trials 10 patient populations More than 200 patients recruited in clinical trials 400 MDs involved in clinical trials More than 70 clinical centers (US, EU, Asia) CE mark filed for first Proof-of- Concept application (STS) 10

11 PII/III in Soft Tissue Sarcomas (STS) Topline Data 11

12 Soft Tissue Sarcoma: epidemiology Sarcomas: a complex family of rare cancers Cancers of the connective tissues are categorized in two major groups: soft tissue sarcoma (STS) and bone sarcoma 60% start in the arms and legs, 30% in the abdomen or torso and 10% in the head or neck. STS develops from the muscles, fibrous tissues, fat, blood vessels, nerves, etc. 50 different subtypes of STS Incidence of sarcomas in 2016: All Study population North America 25,000 9,000 Europe 55,000 20,000 NORTH AMERICA 25,000 cases EUROPE (ALL) 55,000 cases Ref: Datamonitor ref. DMKC

13 Soft tissue sarcoma: patient population 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 Neoadjuvant radiotherapy 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 13

14 Soft Tissue Sarcoma: treatment objectives 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 Surgery 14

15 Randomization Design of Phase II/III study in soft tissue sarcoma Study design STS phase II/III Population: Patients with locally advanced soft tissue sarcoma of the extremity and trunk wall 180 patients recruited 162 patients evaluable Multi center, open-label, randomized trial with active control Test arm NBTXR3 with RTx 50Gy 43 sites 13 countries EU and Asia > 10 STS subtypes 1:1 RTx 50Gy Comparator arm Stratification population: myxoid Lps vs others 15

16 Phase II/III Study in Soft Tissue Sarcoma Flowchart and study design RTx + NBTXR3 (87 patients) RTx (89 patients) Day 1 One time Intratumoral injection End of treatment Surgery Session of RTx according to standard of care (25 x 2 Gy) Surgery Population: Patients with locally advanced soft tissue sarcoma of the extremity and trunk wall Locally advanced soft tissue sarcoma, newly diagnosed or relapsed tumor High risk tumor Unresectable tumor or unfeasible carcinological surgical resection 16

17 Phase II/III study in STS: Endpoints Primary endpoint: Pathological complete response rate (pcrr) as per EORTC Guidelines Secondary endpoints: Safety Operability (surgery margin, R0, ) Pathological Response (pr) Amputation rate Topline data Other exploratory endpoints will be available later 17

18 Two important clinical end points in STS Pathological response & Surgery Margin Primary Endpoint Pathological response 5% viable cells > 5% viable cells Pathological response: % of dead tumor cells Pathological complete response: 95% dead tumor cells ( 5% viable tumor cells) 18

19 Two important clinical end points in STS Pathological response & Surgery Margin Primary Endpoint Pathological response 5% viable cells > 5% viable cells Pathological response: % of dead tumor cells Pathological complete response: 95% dead tumor cells ( 5% viable tumor cells) Secondary Endpoint Surgery (Resection) margin R0 Negative margin 19

20 Pathological response: a direct measure of efficacy Pathological response: % of dead tumor cells Pathological complete response: 95% dead tumor cells ( 5% viable tumor cells) pr: pathological Response Measures the efficacy of cell killing pcrr: pathological Complete Response Rate Measures the optimum efficacy of cell killing Is a potential surrogate for systemic efficacy 20

21 Pathological response as a surrogate for survival Schaefer et al., 2017 pcrr (defined as < 5% viable cancer cells) shows a global trend in relation with OS Unlike in Breast Cancer, pcrr is not significantly correlated with survival in STS given the current state of data 21

22 Surgery / Resection margin: a key endpoint for clinical benefit R0 Negative margin R1 Positive margins R2 Amputation 22

23 R0 / Resection margin increases PFS & OS for patients R0 R1 R2 Resection limits Negative margin Positive margin Amputation Local recurrence-free survival (Local relapse) Negative margin Positive margin Negative margins: R0 surgery significantly correlated to patient benefits like Progression Free Survival (local and distant) and Overall Survival 23

24 Quality of initial surgery (% of patients) Quality of initial surgery (% of patients) R0 Resection margins in Study site in line with French STS Center of Excellence R0 Resection Margin in: Specialized centers 56% Non specialized centers 13% STS Study Control Arm 70 Resection Margin by center 70 Resection Margin in 301 Study R0 R1 R2 Outside NETSARC Non-specialized Center Adapted from Blay et al., 2018 (add full reference Limbs sarcomas operated (n > 240, France) Within NETSARC Specialized Center R0 R1 R2 RT (Control Arm) N=89 24

25 NBTXR3 impact on the standard of care (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 of care Good local tolerance (similar radiation safety in both arms) Manageable acute immunological reaction occurring at the time of injection No impact on planned radiation and surgery *Relative radiation therapy Dose Intensity = (Actual Dose Intensity / Planned Dose Intensity) ITT FAS (Full Analysis Set) 25

26 % of patients with pcr pcrr: the study met its primary end point Pathological Complete Response 16.1 p-value * 7.9 Complete Pathological Response NBTXR3 activated by radiotherapy (N=87) Radiotherapy alone (N=89) More than twice as many patients having a Pathological Complete Response ( 5% viable cells) Statistically significant at an adjusted α of 0,04575 ITT FAS (Full Analysis Set) 26

27 Pathological Response > 90% correlates with superior OS Salah et al. (2018) Meta-analysis on 1663 STS patients Tumor necrosis > 90% following preoperative treatment (i.e. < 10% viable cancer cells) was associated with decreased recurrence risk and superior OS. 27

28 % of patients with R0 resection margins R0 rate: the study also met its secondary endpoint Resection Margin p-value * R0 64 NBTXR3 activated by radiotherapy (N=87) Radiotherapy alone (N=89) Significant 20% relative increase in R0 rate in the NBTXR3 arm Statistically significant at an α of 5% ITT FAS (Full Analysis Set) 28

29 PI quotes Pr. Sylvie Bonvalot, MD, Head of the Sarcoma and Complex Tumor Surgery Unit at Institut Curie, Paris, France and Principal Investigator of the PII/III study commented Data are exceptional and show without any doubt an improvement of radiation therapy impact with a significant number of complete response. NBTXR3 can bring real benefit to patients and it can change the standard of care. This innovation will play a role in many other indications and particularly where radiation is used alone. Pr Jean-Yves Blay, MD, Director of the Centre Léon Bérard, Lyon, France, commented I am amazed by the difference of Response Rate, it is extremely uncommon to double the Rate of Complete histological Response and I do not see any other strategy able to accomplish that. Even more impressive is the R0 rate, which is increased by more than 20% compared to an average rate of 64%. This difference is really impressive, considering that R0 impacts patients relapses and survival. David Raben MD, Professor of Radiation Oncology, University of Colorado Cancer Center, CO, USA, commented: These results from a Phase III study are impressive in a notoriously difficult disease like Soft Tissue Sarcoma. These cancers are generally less sensitive to radiation and previous attempts to improve local control with chemo-radiation regimens were considered too toxic. This study substantiates the medical benefit of safely enhancing the effect of radiation therapy with novel physics-based approaches delivered locally within the cancer. In addition, this product may potentiate a pro-inflammatory environment suitable for immune enabling or DNA damage inhibitor drugs. These findings set the foundation for additional studies in areas such as head and neck cancer and perhaps in areas such as high-risk prostate, bladder or pancreas cancer. 29

30 NBTXR3 Phase II/III 301 study in Soft Tissue Sarcoma Conclusion The trial achieved its primary endpoint pathological Complete Response Rate (pcrr) The trial achieved its secondary endpoint in operability (R0 rate) NBTXR3 demonstrates significant superiority and clinical benefits for patients versus standard of care Safety profile confirmed This randomized trial validated the first in class Mode of Action of NBTXR3 30