Paris-based Nanobiotix is a late clinical-stage nanomedicine company that is spearheading efforts to harness physics rather than biology, as a way to destroy cancer cells.

Founded in 2003 by CEO Laurent Levy, Ph.D., as a spin-off the State University of New York (SUNY) at Buffalo, the company's novel approach uses nanoparticles to boost the effectiveness of cancer treatments such as radiotherapy and, potentially, immunotherapies.

Levy, who has been working in the nanotechnology field for two decades, spoke to Bioscience Technology about the company’s lead product NBTXR3, and how it can enhance radiotherapy for a number of indications currently in clinical trials.

The company’s first foray is into radiotherapy, also known as radiation therapy, and was chosen for a few reasons, Levy said.  For one, it is one of the most widely used treatments in oncology, with 60 percent of all cancer patients receiving radiotherapy during treatment. Secondly, it is a patient population that are usually untapped by the pharmaceutical or biotech companies, so there is a widely open market with a patient population that does not have many treatment opportunities outside of radiotherapy.  Finally, when a physician wants to eradicate a tumor with radiation, the x-ray beam also has to go through healthy tissue too, often causing damage, which limits the dose that can be delivered.

“So the key question is, how can we improve the dose within the tumor, without increasing the dose in surrounding healthy tissue?” Levy said. “We have developed a technology exactly to answer this question.”  

Based on nanotechnology, the company developed an inorganic, crystalline nanoparticle that is 50 nanometers, made with hafnium oxide. This particular material was chosen because it is a highly dense material that has the ability to absorb x-rays. Also, the material is super inert, Levy explained, so it’s able to optimize the benefit/risk ratio for patients.  The benefit being the amount of x-ray absorption, and minimizing the risk by having an inert material with low toxicity.

“So the goal of the company is really to try to transform today’s radiotherapy into nanoradiotherapy,” Levy said. “To make it more efficient and less toxic.”

The company now has a pipeline of seven indications ongoing, including its most clinically advanced which is a Phase 2/3 in soft tissue sarcoma ongoing in Europe and Asia.  They also have two different clinical trials in head and neck cancer patients and one in prostate cancer patients running in the U.S., as well as early clinical trials in liver cancers.

Nanobiotix plans to present data from it's European Phase 1/2 head and neck cancer trial at the American Sociatey of Clinical Oncology (ASCO) Annual Meeting in June.

Levy said that the company has such a wide pipeline because the product has a physical mode of action and potentially could be applied across oncology.

The only change to current patient flow is that patients receive a one-time injection of the nanoparticle, directly into the tumor one day before the first session of radiotherapy. Once the nanoparticles enter tumor cells, they are activated by standard dose of radiation and release a tremendous amount of energy that destroys cancer cells, while preserving the surrounding healthy tissues, which only receive the same dose of radiation as is standard in radiotherapy.

The soft-tissue sarcoma trial is a two-arm trial involving 156 patients, with half receiving radiotherapy alone, and half receiving radiotherapy plus Nanobiotix’s nanoparticles.

At the end of March the Independent Data Monitoring Committee recommended a continuation of the Phase 2/3 trial after completing an interim evaluation of the trial, based on an analysis of the results of two-thirds, or 104 patients.

The primary endpoint in the prospective, randomized, multi-center, open label and active controlled study is the complete pathological response rate. Secondary endpoints include the objective response rate by MRI imaging, evaluation of safety profile, and tumor volume changes.

A full data analysis is expected by the end of 2017, and NBTXR3 could obtain European market approval later this year.

While the company has not disclosed plans for its pathway in the U.S. market, Levy said the company also has one Investigational New Drug application open in the U.S., and its goal is to move forward in the U.S., along with Europe, once it sees more data from its head and neck cancer trial.

Levy believes their novel approach has the potential to impact many cancers.

“From our perspective, we think that the beauty of nanotechnology is that you bring a completely different mode of action into the oncology field,” he said.

With a biological approach, Levy said, one could take hundreds of cancer cells, some of which will be destroyed by chemo, some that will not be destroyed at all because they don’t express the right receptor, and some that will start dying but will then develop some resistance and regrow again.

“When you use physics, you bring something that a cancer cell cannot resist,” he said.

Coming up, Nanobiotix hopes to present more data by mid-year supporting an approach to use their lead product in combination with immuno-oncology drugs.