On March 2, 2021 NANOBIOTIX (Euronext : NANO –– NASDAQ: NBTX – the ‘‘Company’’), a clinical-stage biotechnology company pioneering physics-based approaches to expand treatment possibilities for patients with cancer, reported positive new preclinical data investigating first-in-class radioenhancer NBTXR3, which is being evaluated as a tumor-agnostic, combo-agnostic product candidate across several tumor types (Press release, Nanobiotix, MAR 2, 2021, View Source [SID1234575936]). The data is being shared via poster presentation at the first American Association of Cancer Research (AACR) (Free AACR Whitepaper) Virtual Special Conference on Radiation Science and Medicine, held March 2-3, 2021, by researchers from the University of Texas MD Anderson Cancer Center (MD Anderson).

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PRECLINICAL DATA ON NBTXR3 COMBO

NBTXR3 is composed of sterile, functionalized, crystalline hafnium oxide nanoparticles that are delivered by intratumoral injection one time prior to radiotherapy (XRT). After activation by XRT, the product candidate has a physical primary mechanism of action through which a higher dose of radiation is delivered within the tumor, enhancing the tumor-killing effect of XRT without increasing the dose in surrounding healthy tissues. The subsequent biological secondary mechanism of action that we are evaluating is the potential activation of several immune pathways upon tumor cell destruction, generating adaptive immune response within the body.

NBTXR3 is being evaluated in an expansive global development plan both as a single agent activated by XRT and in combination with other anti-cancer therapies including chemotherapy and immune checkpoint inhibitors. This study examined NBTXR3 activated by XRT in combination with anti-PD-1 along with TIGIT and LAG3 inhibitors in an in vivo anti-PD-1 resistant mouse model (344SQR).

Key Findings Include:

The combination therapy of NBTXR3 + XRT + anti-PD-1 + anti-LAG3 + anti-TIGIT (Combo therapy) significantly promoted the proliferation activity of CD8+ T cells, improved local and distant tumor control, and increased survival rate
The anti-tumor efficacy of the Combo therapy was heavily dependent on CD4+ and CD8+ Tcells
The survivor mice from the groups treated with the Combo therapy were immune to re-injections of tumor cells
The survivor mice maintained significantly higher percentages of memory CD4+ and CD8+ T cells, as well as stronger anti-tumor immune activities than control
The Combo therapy augmented anti-tumor response in both irradiated and unirradiated (abscopal) tumors
POSTER PRESENTATION

Title: Integration of anti-TIGIT and anti-LAG3 with NBTXR3-mediated Immunoradiation Therapy Improved Abscopal Effect and Induces Long-term Memory Against Cancer
Timing: View on-demand starting at 9:30am EST on March 2, 2021 on Virtual Conference platform
Poster Number: PO-040
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About NBTXR3

NBTXR3 is a first-in-class radioenhancer composed of sterile, functionalized, crystalline hafnium oxide nanoparticles. The product candidate is designed to increase the radiotherapy energy deposit inside tumor cells through the nanoparticles’ high atomic number core packaged in the space for interaction with ionizing radiation, and subsequently increase of tumor cell death when compared to radiotherapy alone—without adding toxicity to adjacent healthy tissues. NBTXR3 requires a single, intratumoral administration before the first radiotherapy treatment session, and has the ability to fit into current worldwide standards of radiation care. The primary physical mechanism of action of NBTXR3 activated by radiotherapy could be universal, making it potentially applicable across any solid tumor indication where radiotherapy is a part of standard of care including head and neck, lung, prostate, liver, colorectal, and esophageal cancers. The biological secondary mechanism of action of NBTXR3 activated by radiotherapy has been shown in preclinical studies to prime adaptive immune response, which would potentially bring a new dimension to cancer immunotherapies.