Cancer is a major cause of mortality in the world, and its incidence has been steadily increasing since 1980. According to the World Health Organization (WHO), there will be 15 million new cases of cancer worldwide in 2020. More than 90% of cancer-related deaths occur by the spread of malignant cells to vital organs, a process called metastasis. Pharmaceutical and biotechnology companies are making substantial research investments in order to develop specific treatments that can destroy primary tumors and secondary tumors, i.e. those resulting from metastasis to other organs.
The local treatment of malignant tumors is the cornerstone of cancer treatment, for which standard treatments are surgery and radiotherapy, either used independently or in combination. Radiotherapy has been widely used in most oncology indications for decades. About 60% of cancer patients receive radiotherapy at some point of their treatment regime.
Since radiation must first pass through healthy tissues before reaching the tumor target, radiotherapy treatment is currently limited by toxicity resulting from damage to these healthy tissues. The figure below illustrates the limited therapeutic window concerning the total dose, governing the use of radiotherapy: the more a tumor is radiosensitive, the larger the therapeutic window ; the more healthy tissue is radiosensitive, the greater the risk of permanent damage.
Schematic representation of the therapeutic window of radiotherapy
The fundamental goal of Nanobiotix is to provide a solution to the question of “how to increase the delivered dose to the tumor without increasing it in healthy tissue?” This will lead to a greatly improved efficacy of radiotherapy and most likely increase the overall efficacy of cancer treatment. In this context, Nanobiotix has developed a new, innovative and patented therapeutic approach based on nanoparticles, called ‘NanoXray’.
NanoXray nanoparticles were designed to increase the dose and efficacy of radiotherapy inside the tumor without causing additional damage to surrounding healthy tissues.
Radiotherapy is a local treatment ‘par excellence’ that can change the life-threatening outcome of several cancers, either alone or in combination with other therapeutic approaches. Radiotherapy use ionizing radiation to destroy cancer cells by blocking their capacity to proliferate. The radiation interacts with water molecules in the cell whichin the end generates free radicals killing the cell.
Today, many cancer patients do not receive doses sufficient for tumor destruction, respond insufficiently or not at all to treatments, or even develop resistance to these treatments. Radiotherapy on the opposite is known to be an efficacious – the higher the delivered dose, the better the response. In order to obtain greater radiotherapy efficacy without changing the standard treatment procedures, the dose delivered to the tumor must be increased without increasing its effect on healthy tissues.
The company has developed a disruptive approach for the local treatment of cancer. NanoXray nanoparticles can overcome one of the greatest limitations of radiotherapy: the impossibility of delivering a radiation dose sufficient to reliably destroy the tumor only. At present, this is not feasible because of side effects in the surrounding healthy tissues.
NanoXray nanoparticles were designed to increase the dose and efficacy of radiotherapy inside the tumor without causing additional damage to healthy tissues. Their average size is 50 nm, enabling them to enter and act on cancer cells. They are composed of an inorganic core of crystallized hafnium oxide. The high electron density of this material is in fact the most important feature, enabling a strong interaction with X-rays.
Transmission Electron Microscopy of hafnium oxide nanoparticles (upper left, schematic representation of a nanoparticle)
NanoXray technology has been designed to broaden the therapeutic window by increasing the radiotherapy dose and its effect in the tumor without increasing the dose delivered to healthy tissues (see figure below). The expected result is a significant benefit for the patient in terms of better local control, better tumor response and increased patient survival, depending on the type of cancer treated.
Schematic representation of opening the radiotherapy therapeutic window provided by NanoXray nanoparticles (left: radiotherapy alone; right: radiotherapy in the presence of NanoXray nanoparticles)
NanoXray technology could provide significant progress in radiotherapy. The sum of improvements in the radiotherapy field up to the date does not enable the use of energy doses sufficiently effective to destroy all types of tumors. In reality, the toxicity of treatments for healthy tissues prevents sufficient dose increases and so the tumor escapes control by radiotherapy.
Once injected in the tumor, nanoparticles accumulate in cancer cells as a result of their specific size and the choice of a suitable surface coating. When bombarded with ionizing radiation, the physical properties of hafnium oxide lead to the generation of very large quantities of electrons, thereby considerably amplifying the lethal dose of energy in the tumor. The efficacy of radiotherapy is thus multiplied, while the dose of X-rays passing through healthy tissues remains unchanged.
NanoXray products are made from inert materials and produce an effect only when exposed to radiotherapy.NanoXray largely boosts the efficacy of classical radiotherapy without changing its mode of action, leading to a noteworthy increase in the benefit/risk ratio for the patient.
The benefit/risk ratio will increase and thereby augment the probability of controlling and even destroying the tumor using established radiotherapy guidelines. Nanoparticles in fact provide for a larger quantity of destructive free radicals inside the tumor mass and will increase the efficacy of radiotherapy inside the tumor without augmenting the dose delivered to healthy tissues. It can therefore ultimately target all patients treated with radiotherapy.
Interaction of photons with nanoparticles (high electron density) generates a large number of electrons compared to water (low electron density)
The NanoXray portfolio currently consists of three products designed to meet specific clinical needs for different cancers. They all share the physical mechanism of action described above. The core of the three products is the same; the fundamental difference is the composition of the coating of the nanoparticles and their mode of application. Each of these products is destined for different modes of administration: intra-tumor, intravenous or direct application in the tumor bed during surgery after excising the tumor. The particular NanoXray product will be selected on the basis of specific patient needs defined by the type of cancer, its size, the stage of its course and the optimum moment for therapy, i.e. preoperative, postoperative or no surgery.
NBTXR3 nanoparticles are designed for direct injection into the tumor. The initial indications for NBTXR3 are primary liver cancer, glioblastoma (a specific form of brain cancer), rectal cancer, prostate cancer or head and neck cancers. NBTXR3 is currently clinically tested in patients with soft tissue sarcoma.
NBTX-IV nanoparticles are designed for intravenous injection so that the product can reach the tumor and also the surrounding tissue which may be already invaded locally by cancer cells. This may not only lead to increased tumor destruction but may also reduce the subsequent escape of malignant cells localized in neighboring lymph nodes. Targeted indications are advanced stage tumors that have invaded surroundings lymph nodes, such as rectal cancers, locally advanced prostate cancer or lung carcinoma.
NBTX-TOPO nanoparticles are formulated as a gel to be applied during surgery after removal of the tumor. The product is intended in particular for different types of breast cancer, brain tumors and retroperitoneal soft tissue sarcomas. NBTX-TOPO may be used to delineate the tumor in CT scans and to prepare the tumor bed for postoperative radiotherapy.
NBTXR3, NBTX-IV and NBTX-TOPO are designed to improve anti-cancer treatment of a large number of patients with solid tumors currently treated with radiotherapy (or patients who cannot be treated this way because of their elevated radiosensitivity). The combined use of nanoparticles with radiotherapy will lead to personalized anti-cancer therapy, optimally adapted to the particular features of the tumor in question.
Based on the existing technology and preclinical results, Nanobiotix is developing other nanomedicine programs beyond NanoXray that will sustain its pipeline and will expand the uses of nanoparticles in medicine:
- nanoMag : Magnetic particles for treatment and diagnostic of cancer
- nanoPDT : laser activated nanoparticles for cancer treatment
- Nanobiotix is part of the Sonodrugs European consortium
- Outside oncology field : Business and development collaboration with Malaysian Biotech Corp
Nanobiotix Research Grant Application
Nanobiotix is a young and innovative company wishing to increase its academic network. We are a leading company in the development of nanomedicine and seek collaborations with investigators having overlapping interest.
We are closely collaborating with investigators and it is our intent to support the interest of our investigators to publish the results of our joint research in high ranked scientific journals.
In order to review external ideas in an efficient manner Nanobiotix has established some rules that will help you to prepare a proposal and us to review it in order to provide feedback no later than 6 weeks after receipt of your proposal.
Nanobiotix is open minded in structuring a collaboration to meet the interest of both partners. As such we do not propose a strict framework you need to comply with. In order to start a review process of your proposal please submit a White Paper of 3 pages to Nanobiotix. This document should contain an overview of the scientific background of your request, the objectives of the proposed study and an overview of the experiments you wish to perform. Please also indicate which form of support you are seeking (e.g. materials, funding, etc.). Proposals should be focused on the proposed experiments and the objectives of the collaboration should be achievable in an overseeable period of time.
We will review your proposal and will normally respond to you within 4 weeks, we will in no case exceed 6 weeks. We may ask you to participate a question/answer session and also to present face-to-face during the review process. Once your proposal has been approved the signing of a collaboration agreement with your institution is mandatory for Nanobiotix to initiate the research.
In exchange for our support Nanobiotix expects you to regularly prepare reports and to benefit from access to intellectual property, research results… etc.
Please be aware that Nanobiotix accepts all international and national requirements governing our research and development work. We expect you to adhere to the applicable guidelines and regulations as well.
Nanobiotix is willing to support direct funding and will also cover indirect costs. In an order to balance the direct and indirect contributions and to have a consistent balance of the indirect costs within the different territories across the globe Nanobiotix has decided that it will not support funding scheme with indirect costs exceeding 25%.
Should this meet your expectations please submit your White Paper to firstname.lastname@example.org.