Laurent Levy, CEO
France’s Nanobiotix (Euronext:NANO) is hoping to change the paradigm for cancer treatment with a single nanomedicine applicable across oncology for millions of patients.
“What differentiates us is that we do not use biology or chemistry, but rather physics to destroy cancer cells, and activate the immune system.” CEO, Laurent Levy, says in an interview with BioTuesdays.
“We have a broad ongoing clinical development program underway in seven cancer indications in the EU, U.S. and Asia and hope to receive our first EU market approval in soft tissue sarcoma later this year,” he adds.
Mr. Levy says Nanobiotix targets radiation therapy - one of the largest oncology markets with minimal competition. “We are developing solutions designed to solve the issue of improving the energy dose from radiation within the tumor but without increasing damages in healthy surrounding tissue.”
He explains that the company’s lead therapy, NBTXR3, has been designed to maximize x-ray absorption within the tumor. “We have nanosized it to 50 nanometers to enter the cell, to strongly absorb x-rays and to be non-toxic,” he contends. “Our IP covers 11 patent families, with protection until at least 2029.”
50 nanometer HfO2* particles were chosen because they have the best ratio for X-ray absorption and non-toxicity
According to Mr. Levy, NBTXR3 plus radiotherapy demonstrates a universal physical mechanism of action both locally, for primary tumor destruction, and to generate immunogenic cell death potentially to harness immune generating systemic activity.
“NBTXR3 has a physical mode of action that could work across all solid tumors to enhance the efficacy of radiotherapy alone with standard of care or in combination with immunoncology, chemotherapy and PARP inhibitors,” he adds. “Only one administration of NBTXR3 is required before the first radiotherapy session.”
As a single agent, Nanobiotix is developing NBTXR3 for the treatment of soft tissue sarcoma, head and neck cancer alone and in combination with chemotherapy, liver metastasis, hepatocellular cancers and prostate cancer. And, in combination with checkpoint inhibitors, the company is pursuing recurrent head and neck cancer and lung metastasis.
NBTXR3 has a physical mode of action: Increase dose absorption & deposition in the tumor
In an ongoing Phase 1/2 in elderly and frail patients with head and neck cancer, Mr. Levy says NBTXR3 presented in June 2017 at ASCO, an excellent safety profile, with no serious adverse events related to NBTXR3, which is a “huge asset in this frail population.”
In addition, 10-out-of-11 patients responded to treatment, with seven complete responses, “meaning that the tumor is completely gone and quality of life improved.” Mr. Levy also points out that all patients had prolonged response and survival at higher dose levels.
“These three pillars – overall survival, low toxicity and quality of life – represent the holy grail of oncology,” he adds. “That’s why we are going full speed ahead in this indication where we could have an opportunity to bring this to patients.”
As a result, Nanobiotix has amended the trial’s protocol to include 44 additional patients and new clinical sites in Europe to speed up recruitment. An update on data is expected in mid-2018 to confirm the potential value of NBTXR3 in head and neck cancer.
Mr. Levy says that when the company obtains further data, the plan is to approach the FDA to discuss the regulatory path forward of NBTXR3 in head and neck cancer.
In soft tissue sarcoma, Nanobiotix has completed recruitment in a pivotal trial of NBTXR3, with top-line data expected around the end of the second quarter of 2018.
“The value of NBTXR3 is to go forward in head and neck cancer but our strategy is to get approval initially in soft tissue sarcoma,” Mr. Levy points out. “We can’t assume that we will get the amount of clinical benefits and reimbursement in soft tissue sarcoma that we could get in head and neck cancer because of the nature of the population we are treating. So we plan use the head and neck data to seek reimbursement first before expanding it to soft tissue sarcoma in later stage.”
The company’s European Phase 2/3 soft tissue sarcoma study of the extremity and trunk wall has completed enrollment of more than 156 patients in 12 countries, with topline data scheduled for release at the end of the second quarter of 2018. Top line data will be focusing on the endpoints, which are complete path response rate, and operability, which is critical for those patients and related to better survival. Full data will be presented in medical conference later.
“We do not plan, for now, to pursue this indication in the U.S., where our focus will be head and neck and prostate cancer, and combining NBTXR3 with immunoncology,” Mr. Levy says.
To test its theory of combining NBTXR3 with immunoncology, Nanobiotix sampled 40 of the 156 patients in the Phase 2/3 soft tissue sarcoma trial. The comparative study measured 20 patients treated with NBTXR3 plus radiotherapy against 20 patients with radiotherapy alone to determine whether there was an increase in CD8 cells, which represents a marker for the immune system’s cytotoxic T-cells.
“What we found was an increase number of patients with CD8 infiltration, compared with radiation therapy alone. Also, a significant up regulation of Immune checkpoint inhibitor and adaptive immune response-related genes has been observed, which could indicate the potential of NBRXR3 to increase the response rate in patients and the quality of response of multiple checkpoint inhibitors,” Mr. Levy contends.
Of the four checkpoint inhibitors approved for use in head and neck cancer and non-small cell lung cancer - Opdivo, Keytruda, Tecentriq and Imfinzi –around 20% to 25% of patients respond to treatment, he points out. Nevertheless, the four drugs are expected to generate $15-billion in revenue by 2024 in the two indications.
The immune system uses checkpoints on certain immune cells that need to be activated to start an immune response. Cancer cells, however, find ways to use these checkpoints to avoid being attacked by the immune system. Checkpoint inhibitor drugs that target these checkpoints have become an important element in the immunotherapy arsenal.
In the next few months, Nanobiotix plans to dose the first patients in Phase 1/2 trial in patients with advanced head and neck cancer and non-small cell lung cancer that do not respond to checkpoint inhibitors. The goal of the dose escalation and dose expansion study is to transform non-respondent patients into responders, with NBTXR3 activated by radiotherapy and checkpoint inhibitors.
For example, Mr. Levy suggests that for every 10 cancer patients, around two will respond to checkpoint inhibitors. “If two of the remaining eight patients respond to our treatment, we will have doubled the current rate of response to checkpoint inhibitors. If we can achieve better response and survival, our product can have an important impact, if not the main impact, in the checkpoint market in these two indications.”
A leading pipeline of nanomedicines in oncology
via Features | BioTuesdays by Kilmer Lucas IR https://ift.tt/2rH6jxg