On April 11, 2022 NANOBOTIX (Euronext : NANO –– NASDAQ: NBTX – the ‘‘Company’’), a clinical-stage biotechnology company pioneering physics-based approaches to expand treatment possibilities for patients with cancer, reported new data from an open-label preclinical study evaluating the combination of first-in-class radioenhancer, NBTXR3, with the triple blockade of PD-1, LAG-3, and TIGIT ("Combination therapy") (Press release, Nanobiotix, APR 11, 2022, View Source [SID1234611962]). The data were published via E-Poster presentation at the 2022 Annual Meeting of the American Association of Cancer Research (AACR) (Free AACR Whitepaper), held April 8-13, 2022, by researchers from The University of Texas MD Anderson Cancer Center (MD Anderson).
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"We believe that the potential immune priming effect of radiotherapy-activated NBTXR3 could prove to be a game-changer for cancer immunotherapy," said Laurent Levy, co-founder and chairman of the executive board at Nanobiotix. "Our view is that while new immunotherapy treatment modalities with the potential to improve outcomes for patients continue to emerge, they remain reliant upon an underlying immune response. This new preclinical gene expression data showing that the addition of NBTXR3 enhanced activity in key immune pathways associated with innate and adaptive immunity, and outperformed all other combinations in efficacy, survival, and induction of long-term anti-cancer memory, adds to a growing body of support for NBTXR3 as a product candidate that could potentially help expand the benefits of immunotherapy to larger share of the patients we serve."
PRECLINICAL DATA ON IMMUNOTHERAPY BLOCKADE PLUS RADIOTHERAPY-ACTIVATED NBTXR3
Previously reported preclinical and clinical data evaluating NBTXR3 in combination with diverse immune checkpoint inhibitors (ICIs) including anti-PD-1, anti-CTLA-4, anti-LAG-3, and anti-TIGIT suggest that, after activation by radiotherapy, the radioenhancer may induce an "immune priming" effect that could help improve and expand the benefits of ICIs to more patients.
This new analysis, presented at AACR (Free AACR Whitepaper), assessed immune gene expression associated with multiple combinations of NBTXR3, anti-PD-1, anti-LAG-3, and anti-TIGIT.
Key Findings Include:
The Combination therapy outperformed all other tested treatment regimens in efficacy, survival, and induction of long-term anti-cancer memory
The Combination therapy significantly promoted the upregulation of mRNA transcripts involved in innate immunity, the humoral response, B cell function, dendritic cell function, and antigen processing within primary, irradiated tumors relative to untreated controls
Within non-irradiated tumors, the Combination therapy produced elevations in multiple immune-related pathways that were significantly higher than those produced by other treatment combinations and these pathways included both adaptive and innate immunity; B, T, natural killer, and dendritic cell function; and antigen processing
The Combination therapy promoted immune activation at the irradiated site, abscopal immune responses are improved with the addition of LAG-3 and TIGIT to PD-1 and radiotherapy-activated NBTXR3, and the data suggest that the Combination therapy may be effective against metastatic cancers
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About NBTXR3
NBTXR3 is a novel, potentially first-in-class oncology product, composed of functionalized hafnium oxide nanoparticles that is administered via one-time intratumoral injection and activated by radiotherapy. The product candidate’s physics-based mechanism of action (MoA) is designed to induce significant tumor cell death in the injected tumor when activated by radiotherapy, subsequently triggering adaptive immune response and long-term anti-cancer memory. Given the MoA, Nanobiotix believes that NBTXR3 could be scalable across any solid tumor that can be treated with radiotherapy and across any therapeutic combination, particularly, with immune checkpoint inhibitors.
NBTXR3 is being evaluated in locally advanced head and neck squamous cell carcinoma (HNSCC) as the primary development pathway. The company-sponsored phase I dose escalation and dose expansion study has produced favorable safety data and early signs of efficacy. In February 2020, the United States Food and Drug Administration granted regulatory Fast Track designation for the investigation of NBTXR3 activated by radiation therapy, with or without cetuximab, for the treatment of patients with locally advanced HNSCC who are not eligible for platinum-based chemotherapy.
Nanobiotix has also prioritized an Immuno-Oncology development program—beginning with a Company sponsored phase I clinical study, evaluating NBTXR3 activated by radiotherapy in combination with anti-PD-1 checkpoint inhibitors for patients with locoregional recurrent or recurrent/metastatic HNSCC and for patients with lung or liver metastases from any primary cancer eligible for anti-PD-1 therapy, either naïve or resistant to prior PD-1 (either primary or secondary as per SITC (Free SITC Whitepaper) criteria).
Given the Company’s focus areas, and balanced against the scalable potential of NBTXR3, Nanobiotix has engaged in strategic collaborations to expand development of the product candidate in parallel with its priority development pathways. Pursuant to this strategy, in 2019 Nanobiotix entered into a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center to sponsor several phase I and phase II studies to evaluate NBTXR3 across tumor types and therapeutic combinations. In 2021, the Company entered into an additional strategic collaboration agreement with LianBio to support its global phase III study in Asia along with four future registrational studies.