NANOBIOTIX announced the final readout on primary endpoints from Study 102 Dose Expansion?the expansion part of a Phase 1 dose escalation and dose expansion study evaluating potential first-in-class radioenhancer NBTXR3 for patients with locally advanced head and neck cancer (Study 102). The results were presented by Principal Investigator Professor Christophe Le Tourneau in an oral presentation at the 65th Annual Meeting of the American Society for Radiation Oncology (ASTRO). Additionally, the abstract was selected for inclusion in a scientific highlight session on head and neck cancer and the final results were selected for discussion in a scientific discussion on augmenting the potential of radiation therapy (RT) with novel therapeutics and imaging.

This oral presentation at ASTRO will be followed by a conference call on October 5, 2023, at 8:00 AM EDT /2:00 PM CEST. During the call, Laurent Levy, chief executive officer, will review the Study 102 final data before taking questions from participants. Study 102 was designed as a multicenter Phase 1 study with a dose escalation part followed by a cohort expansion to further test the recommended phase II dose.

The escalation part achieved its primary objective, establishing a tolerable safety profile without dose-limiting toxicities and a recommended phase 2 dose (RP2D) at 22% of tumor volume. The completed cohort expansion recruited a total of 56 patients across 20 sites in 4 European countries. In each patient, the primary tumor was injected with NBTXR3, while involved lymph nodes were not injected.

The NBTXR3-injected lesion and the non-injected lesion were treated with the same dose of intensity-modulated radiation therapy (IMRT). The patient population entered the study with negative prognostic factors such as advanced age, and a high burden of comorbidity as measured by the age-adjusted Charlson Comorbidity Index (ACCI = 4)2. 61% of patients in the study were aged = 70 years and 67% had ACCI ³ 4. The median duration of follow up was 18.2 months. All 56 patients treated received at least 90% of the planned injected volume of NBTXR3 and 91% completed IMRT.

5 patients discontinued IMRT due to treatment-emergent adverse events (TEAEs), of which one TEAE (sepsis) was possibly related to RT and NBTXR3. 10 deaths occurred within 180 days of enrollment, of which 1 death (sepsis) was possibly related to RT and NBTXR3. 80% of these patients (8/10) entered the study with a high burden of comorbidity (ACCI ³ 4).

The study concluded that injection of NBTXR3 followed by RT activation was feasible and well tolerated in elderly patients with LA-HNSCC. The evaluable population in the study included 44 patients. Response was measured in the NBTXR3-injected lesion alone (injected lesion) as per RECIST 1.1, and in the NBTXR3-injected and non-injected lesions together (all lesions).

In the injected lesions, data showed an overall response rate (ORR) of 81.8% (36/44) with a complete response rate (CRR) of 63.6% (28/44). In all lesions, data showed an overall response rate of 79.5% (23/44) with a complete response rate of 52.3% (23/44). At the final readout, an independent review committee determined a median Progression-Free Survival (mPFS) of 16.9 months in evaluable patients.

Median Overall Survival (mOS) in evaluable patients was 23.1 months. Historical data in a similar population show an expected mPFS of 9 months and mOS of 12 months3. Importantly, the median duration of response in NBTXR3-injected lesions was not reached by the end of the study, compared to a median duration of response of 12.4 months in all lesions, suggesting durable antitumor activity from RT-activated NBTXR3.

To date, the Company has provided timing expectations for NANORAY-312 informed by initial hypotheses within the study protocol, including recruitment rate projections and an expected ?Time-to-Event? (e.g., tumor progression, death, etc.) for patients based on historical data in a similar population (i.e., 9-month mPFS and 12-month mOS). After observation of a potentially significant extension in mPFS and mOS versus historical data in the final efficacy analysis of Study 102, and in view of experience with global recruitment ramp up since the beginning of site activation for NANORAY-312, Nanobiotix is adjusting guidance for the NANORAY-312 futility analysis to 2H2024.

The Company expects NANORAY-312 to record the appropriate number events for the interim readout in 1H2025, and to deliver the interim efficacy analysis mid-2025.