Slides
Page 1
CONFIDENTIAL 1 Immunorad September 2025 Data on Phase 1 Trial Safety and preliminary efficacy of NBTXR3/SBRT in combination with Immune Checkpoint Inhibitors in anti-PD-1 resistant patients with melanoma treated in the phase I trial Study 1100 Cohort 3 – Melanoma Subgroup Analysis Jason W. Chan, MD, Ari Rosenberg, MD, Alexander Lam, MD, James Lee, MD, Adil Daud, MD, William A. Stokes, MD,Nabil F. Saba, MD, Frances Collichio, MD, Hyeon Yu, MD, Priya Mody, MD, Jared Weiss, MD, Stergios Moschos, MD,Steven Powell, MD, Shannon Peck, MD, Michele Lohr, MD, Ellen A. Redstone, MD, Zhenteng Li, MD, David Rolando,Romain Gineste, PhD, Omar I. Vivar, PhD, Aditya Juloori, MD, Colette Shen, MD, PhD
Page 2
2 Important notice regarding forward-looking statements IMPORTANT: You must read the following before continuing. References herein to this presentation (the “Presentation”) shall mean and include this document, the oral presentation accompanying this document provided by Nanobiotix SA (the "Company" and, together with its 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 matter contained herein. This Presentation has been prepared by the Company and is provisional and for information purposes only. The information has not been subject to independent verification and is qualified in its entirety by the business, financial and other information that the Company is required to publish in accordance with the rules and regulations applicable to companies listed on the Nasdaq Global Select Market and the regulated market of the Euronext in Paris and the requirements of the U.S. Securities and Exchange Commission (the "SEC") and the French Financial Markets Authority (Autorité des Marchés Financiers -- the "AMF"), including the risk factors described in the Company's most recent universal registration document filed with the AMF and the most recent Annual Report on Form 20-F filed with the SEC, as updated from time to time by the Company's other public reports including the most filed recent half-year report (together the “Report”), which are available free of charge on the Company's website (www.nanobiotix.com) and the respective websites of the AMF (www.amf-france.org) and the SEC (www.sec.gov). The Presentation contains certain forward-looking statements, including within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. All statements in the Presentation other than statements of historical fact are or may be deemed to be forward looking statements. These statements are not guarantees of the Company’s future performance. When used in the Presentation, the words “anticipate,” “believe,” “can,” “could,” “estimate,” “expect,” “intend,” “is designed to,” “may,” “might,” “plan,” “potential,” “predict,” “objective,” “shall,” “should,” “will,” or the negative of these and similar expressions identify forward-looking statements. These forward-looking statements relate without limitation to the Company’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. Such statements reflect the current view of the Company's management and 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, including, but not limited to, those identified under “Risk Factors” in the Report. These risks and uncertainties include factors relating to: our ability to successfully develop and commercialize NBTXR3, including through the License Agreement by and between Janssen Pharmaceutica NV and Nanobiotix, dated July 7 2023 (the “Janssen Agreement”); our ability to complete clinical trial NANORAY-312 within the expected time-frame due to a number of factors, including delays in patient enrollment or in manufacturing sufficient quantities of NBTXR3 necessary to conduct the trial in a timely manner; our ability to expand our product pipeline by developing and commercializing NBTXR3 in additional indications, including in combination with chemotherapies or I-O treatment; Our ability to complete applicable pre-marketing regulatory requirements and/or our ability to maintain regulatory approvals and certifications for our products and product candidates and the rate and degree of market acceptance of our product candidates, including NBTXR3;our ability about the initiation, timing, progress and results of our preclinical studies and clinical trials, including those trials to be conducted under our collaborations with the MD Anderson Cancer Center of the University of Texas (“MD Anderson”); our ability to obtain raw materials and maintain and operate our facilities to manufacture our product candidates, to market and distribute our products upon successful completion of applicable pre-marketing regulatory requirements, specifically NBTXR3; our reliance on Janssen to conduct the NBTXR3 co-development and commercialization activities in accordance with the Janssen Agreement, including the potential for disagreements or disputes; the risk that Janssen may exercise its discretion in a manner that limits the resources contributed toward the development of NBTXR3; and the ability of Janssen to exercise its termination rights under the Janssen Agreement without cause; our ability to obtain funding for our operations. In light of the significant uncertainties in these forward-looking statements, these statements should not be regarded or considered as a representation or warranty by the Company or any other person that the Company will achieve its objectives and plans in any specified time frame or at all. Even if the Company’s performance, including its financial position, results, cash-flows and developments in the sector in which the Company operates were to conform to the forward-looking statements contained in this Presentation, such results or developments cannot be construed as a reliable indication of the Company’s future results or developments. The Company expressly declines any obligation to update or to confirm any prospective information in order to reflect an event or circumstance that may occur after the date of this Presentation. The Presentation and any information do not constitute an offer to sell or subscribe or a solicitation to purchase or subscribe for securities, nor shall there be any sale of these securities in the United States or any other jurisdiction 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 of securities may be conducted in any member state of the European Economic Area (including France) prior to the publication in the relevant member state of a prospectus that complies with the provisions of Regulation 2017/119. The Presentation includes information on the use of the Company’s products and its competitive position. Some of the information included in the Presentation 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 data comes from the Company’s own internal research and estimates based on the knowledge and experience of the Company’s management. While Nanobiotix 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 Presentation. Caution should be exercised when interpreting results from separate trials involving separate product candidates. There are differences in the clinical trial design, patient populations, and the product candidates themselves, and the results from the clinical trials of distinct product candidates may have no interpretative value with respect to our existing or future results. Similarly, caution should be exercised when interpreting results relating to a small number of patients or individually presented case studies. The Presentation should be read with the understanding that the Company’s actual future results may be materially different from what is expected. The Company qualifies all of the forward-looking statements by these cautionary statements. All persons accessing the Presentation are deemed to agree to all the limitations and restrictions set out above.
Page 3
CONFIDENTIAL 3 Study 1100 – Expansion Cohort 3 – Melanoma Extract Study objective: RP2D and safety HNSCC- Cohort 1 HNSCC- Cohort 2 Lung/ Liver/ Soft tissue Mets- Cohort 3 The same as Cohort 1 except: Naïve to prior anti-PD-1/ anti-PD-L1 Inoperable LRR or R/M HNSCC Tumor to be injected is in HN region, lungs, or liver or soft tissue Resistant to prior anti-PD-1/ anti-PD-L1 Primary tumor must be originating from any solid tumor that is: Resistant to a prior anti-PD-1/ anti-PD-L1 Tumor to be injected is in lung, liver, or soft tissue Melanoma Extraction Study Treatments Objectives and Endpoints Day 1: One- time pre-med steroid then NBTXR3 IT injection (% of baseline) Day 7-16: Begin tumor-site specific RT (35-45Gy in 3-5 fractions) Day after RT: Begin or Resume PD-1 (pembrolizumab or nivolumab) Primary: Recommended Phase 2 Dose Secondary: ORR, Safety and Feasibility, and Body-Kinetics Exploratory: Survival Outcomes, Duration of Responsibility, and Biomarkers of Response
Page 4
CONFIDENTIAL 4 Treating Melanoma Patients After Multiple Lines of Treatment1 Study 1100 third cohort results: Focus on melanoma 1 Lim SY, et al. The molecular and functional landscape of resistance to immune checkpoint blockade in melanoma. Nat Commun. 2023 Mar 18;14(1):1516. doi: 10.1038/s41467-023-36979-y. PMID: 36934113; PMCID: PMC10024679. 2 Ascierto, et al. (2017). Initial efficacy of anti-lymphocyte activation gene-3 (anti–LAG-3; BMS-986016) in combination with nivolumab ( nivo) in pts with melanoma (MEL) previously treated with anti–PD-1/PD-L1 therapy.. Journal of Clinical Oncology. 35. 9520-9520. 10.1200/JCO.2017.35.15_suppl.9520. Resistance to immune checkpoint inhibitor in melanoma is common and remains a clinical challenge “This patients represent one of the more difficult clinical challenges […] as many have exhausted standard therapies” Colette Shen, MD, PhD, Assistant Professor of Radiation Oncology, University of North Carolina Lineberger Comprehensive Cancer Center Primary and secondary resistance to anti-PD-1 therapy occurs in ~50% and ~25% of melanoma patients In this resistant patient population and with no standard approach, response rate is generally low (e.g. 20% ORR and 50% DCR respectively2)
Page 5
CONFIDENTIAL 5 Baseline Characteristics of Melanoma Patients Cut-Off: 21 Aug 2025 Melanoma primary cancer diagnosis N = 21 Median age, years (Min-Max) 63 (29 - 90) Gender, n (%) Male 14 (66.7) ECOG, n (%) 0 -1 20 (95.2) Lactate dehydrogenase level, n (%) Unknown 2 Above normal range 4 (21.1) Within normal range 15 (78.9) Median number of lesions (Min-Max) 3 (1 - 22) Clinical stage group at study entry, n (%) III 10 (47.6) IV 11 (52.4)
Page 6
CONFIDENTIAL 6 Safety Radiation, PD1, Injection, NBTXR3 No Grade 4-5, No SAEs
Page 7
CONFIDENTIAL 7 Patients Failed Multiple Treatment Lines Prior Entering The Study Melanoma patients, N=19 Melanoma Patient Anti-PD-1 Anti CTLA4 Anti-LAG3 TLR9 agonist TIL BRAFi MEKi RANKLi ATRi TVEC CT? Prior RT 1 PD 2 PD PD 3 PD PD PD PD 4 PD 5 PD PD PD PD 6 PD PD PD 7 PD PD 8 PD PD 9 PD 10 PD PD 11 PD PD PD 12 PD PD 13 PD PD PD PD 14 PD PD PD PD PD PD 15 PD PD PD PD 16 PD PD PD PD 17 PD PD 18 PD 19 PD PD PD
Page 8
CONFIDENTIAL 8 Patients Resistant to Anti-PD1 and Multiple Line of Treatments Multi-resistance patient population Cut-Off: 21 Aug 2025 SITC definition of primary resistance: Occurs when a patient receives adequate exposure to a PD-1 or PD-L1 inhibitor (usually ≥ 6 weeks or 2–3 doses), yet fails to achieve any objective clinical benefit (i.e., no partial response [PR] or better) and disease progression is confirmed on follow-up imaging . Melanoma primary cancer diagnosis N = 21 Prior immunotherapies, n (%) Anti-PD-1 21 (100) Anti-CTLA4 11 (52.4) Anti-LAG3 7 (33.3) TVEC 5 (23.8) Other 2 (9.5) Prior BRAF/MEK therapy, n (%) 2 (9.5) Prio other systemic treatment, n (%) 3 (14.3) Prior RT, n (%) 5 (23.8)
Page 9
CONFIDENTIAL 9 Best Sum of Target Lesion Diameter Change from Baseline 1100 study, primary melanoma evaluable subjects Waterfall – Best Sum Target of Lesion Change – N=19 Cut-Off: 21 Aug 2025 19 evaluable patients 2 patients were non-evaluable as post-treatment imaging at the date of the data cut-off were still pending
Page 10
CONFIDENTIAL 10 Efficacy (RECIST 1.1): 47.4% of ORR *2 patients were non-evaluable as post-treatment imaging at the date of the data cut-off were still pending 1 patient received additional SBRT on target lesions without JNJ-1900.This patient didn’t show response at the date of the cutoff. Cut-Off: 21 Aug 2025 ORR is 47.4% DCR is 78.9% Evaluable for Efficacy Primary melanoma N=19* Overall response by number of lesions at baseline Injected response 1-4 (N = 14) 5+ (N = 5) All (N = 19) All (N = 19) CR 4 (28.6) 0 4 (21.1) 5 (26.3) PR 4 (28.6) 1 (20.0) 5 (26.3) 5 (26.3) SD 3 (21.4) 3 (60.0) 6 (31.6) 9 (47.4) PD 3 (21.4) 1 (20.0) 4 (21.1) 0 ORR (= CR + PR) 8 (57.1) 1 (20.0) 9 (47.4) 10 (52.6) 95% CI [28.9 - 82.3] [0.5 - 71.6] [24.4 - 71.1] [28.9 - 75.6] DCR (= SD + CR + PR) 11 (78.6) 4 (80.0) 15 (78.9) 19 (100) 95% CI [49.2 - 95.3] [28.4 - 99.5] [54.4 - 93.9] [82.4 - 100]
Page 11
CONFIDENTIAL 11 Treatment Outcome After Each Prior Treatment, and After NBTXR3/RT Melanoma patients, N=19 Melanoma Patient Anti-PD-1 Anti CTLA4 Anti-LAG3 TLR9 agonist TIL BRAFi MEKi RANKLi ATRi TVEC CT? Prior RT NBTXR3/RT 1 PD → SD 2 PD PD → CR 3 PD PD PD PD → PD 4 PD → CR 5 PD PD PD PD → PR 6 PD PD PD → CR 7 PD PD → PD 8 PD PD → PR 9 PD → PR 10 PD PD → CR 11 PD PD PD → PR 12 PD PD → SD 13 PD PD PD PD → PD 14 PD PD PD PD PD PD → SD 15 PD PD PD PD → PD 16 PD PD PD PD → SD 17 PD PD → SD 18 PD → SD 19 PD PD PD → PR OR (RECIST 1.1)
Page 12
12 Local Response Linked to Systemic Activity 1100 study, primary melanoma NBTXR3-injected evaluable subjects Treatment Response – Best Individual Target Lesion – N=19 Best individual target lesion diameter change from baseline Cut-Off: 21 Aug 2025 19 evaluable patients. 2 patients were non-evaluable as post-treatment imaging at the date of the data cut-off were still pending
Page 13
13 Early signs of efficacy: 14.6 months Median Overall Survival 1100 study, all treated melanoma subjects – Early data, OS under maturation All Patients: N=21 Cut-Off: 21 Aug 2025 14.6 months mOS (IC95: 11.6 - NR)
Page 14
14 Patient Case: Melanoma Patient, 81 yo, Refractory to ICI (Part 2) Dose level 33% GTV – Still in study Stable patient NRAS-mutant cutaneous melanoma Patient Case : RECIST Best Overall Response SD – Response Ongoing For 19 Months, Patient Still On Study FDG PET/CT for Local Response Prior to study entry, patient progressed on multiple lines of treatment: Pembrolizumab monotherapy, Ipilumimab monotherapy, RT (pelvis/R adrenal 40 Gy/10fx in 2020) LXH254 trial (BRAF and CRAF inhibitor), relatlimab/nivolumab
Page 15
15 Patient Case: Melanoma Patient, 81 yo, Refractory to ICI (Part 2) Dose level 33% GTV – Still in study Stable patient NRAS-mutant cutaneous melanoma Patient Case : RECIST Best Overall Response SD – Response Ongoing For 19 Months, Patient Still On Study FDG PET Post RT (6 weeks post RT) FDG PET/CT for Local Response Prior to study entry, patient progressed on multiple lines of treatment: Pembrolizumab monotherapy, Ipilumimab monotherapy, RT (pelvis/R adrenal 40 Gy/10fx in 2020) LXH254 trial (BRAF and CRAF inhibitor), relatlimab/nivolumab RT 40Gy/10Fx
Page 16
16 Patient Case: Melanoma Patient, 81 yo, Refractory to ICI (Part 2) Dose level 33% GTV – Still in study Stable patient Post-NBTXR3+ re-irradiation to right adrenal (35 Gy/5Fx) NRAS-mutant cutaneous melanoma Patient Case : RECIST Best Overall Response SD – Response Ongoing For 19 Months, Patient Still On Study FDG PET Post RT (6 weeks post RT) Pre-NBTXR3/RT FDG PET/CT for Local Response Prior to study entry, patient progressed on multiple lines of treatment: Pembrolizumab monotherapy, Ipilumimab monotherapy, RT (pelvis/R adrenal 40 Gy/10fx in 2020) LXH254 trial (BRAF and CRAF inhibitor), relatlimab/nivolumab Study 1100RT 40Gy/10Fx
Page 17
17 Patient Case: Melanoma Patient, 81 yo, Refractory to ICI (Part 2) Dose level 33% GTV – Still in study Stable patient Post-NBTXR3+ re-irradiation to right adrenal (35 Gy/5Fx) Stable Disease BOR per RECIST, however PET scan suggests Complete Metabolic Response NRAS-mutant cutaneous melanoma Patient Case : RECIST Best Overall Response SD – Response Ongoing For 19 Months, Patient Still On Study FDG PET Post NBTXR3/RT (4 weeks post RT and start of anti-PD-1) FDG PET Post RT (6 weeks post RT) Pre-NBTXR3/RT FDG PET/CT for Local Response Prior to study entry, patient progressed on multiple lines of treatment: Pembrolizumab monotherapy, Ipilumimab monotherapy, RT (pelvis/R adrenal 40 Gy/10fx in 2020) LXH254 trial (BRAF and CRAF inhibitor), relatlimab/nivolumab Study 1100 NBTXR3+SBRT 35Gy/5F +anti-PD-1 RT 40Gy/10Fx
Page 18
18 Conclusion for NBTXR3 in Metastatic Melanoma NBTXR3 could represent a new option in this patient population • NBTXR3 injection in a single melanoma lesion at the RP2D dose (33% of the GTV) was feasible and well tolerated • NBTXR3/RT was also well tolerated in combination with anti-PD-1 • Promising local and systemic control observed with: • 47.4% ORR as per RECIST 1.1 in evaluable patients • 100% DCR in injected lesions, and 78.9% overall • Early analysis of OS shows a Median OS of 14.6 months in the all treated population With promising preliminary efficacy results, this data warrants further evaluation of NBTXR3/RT in combination with ICI in a randomized trial