AGuIX®: an innovative nanodrug with the aim to improve radiotherapy treatment of cancer

Radiotherapy: the future of cancer treatment

Widely used for decades, radiotherapy is considered one of the reference treatments for cancer: 60% of cancer patients are treated with radiotherapy at some stage of their treatment. With an expected increase of 16% in the number of patients treated by 2025, radiotherapy has become a permanent fixture in the oncology landscape, supported particularly by numerous possibilities for development with image-guided radiotherapy or in combination with immunotherapy.

Nanoparticles for precision radiotherapy: combining diagnosis and treatment

NH TherAguix has developed an innovative theranostic* approach in nanomedicine: designed to increase the dose and efficacy of radiotherapy within the tumor itself without increasing damage to healthy tissue, AGuIX® also allows for very precise guidance by imaging. NH TherAguix aims to make AGuIX® a new standard of care in oncology in the field of precision radiotherapy.

* Theranostic is an approach that uses imaging to map cancer in the body and treat them in a targeted manner.

AGuIX®: a technological platform resulting from 10 years of research

Recognized by the international scientific community through more than 70 scientific publications and 14 patent families, AGuIX® technology is based on the use of nanoparticles composed of gadolinium, an element already well known for its magnetic properties and used as a positive contrast agent for MRI since 1986. In addition to its magnetic properties, gadolinium has a high atomic number (Z = 64) allowing for a very strong interaction with X-rays. Once inside the tumor, it makes it more sensitive to X-rays, thus increasing the effectiveness of radiotherapy even though the dose of X-rays passing through normal tissue remains unchanged.

The triple action of AGuIX®: due to its characterisation, AGuIX® fits perfectly with the standard of care

Thanks to its nanometric structure, which allows administration by intravenous injection, and to its active principle, AGuIX® combines essential assets for fighting tumors (targeting, imaging and treatment) and is part of the theranostic concept, i.e. combining therapy (radiosensitizing effect) with diagnosis (MRI imaging).

The size of the AGuIX® nanoparticle allows it, once injected, to accumulate preferentially in tumors characterized by a porous vascular network, and not in healthy tissues, while presenting a rapid renal clearance, thus avoiding toxicity problems.

Strong proof of concept

The first human study was conducted during the NANORAD 1 Phase 1b trial between 2016 and 2019. This study evaluated AGuIX® in terms of (i) tolerance after intravenous injection, (ii) MRI contrast uptake and (iii) initial evidence of radiosensitization, when combined with the standard pan-brain radiotherapy protocol for patients with brain metastases.

Beyond the safety and pharmacokinetic aspects of this trial, NANORAD 1 has validated the triple action of AGuIX®, i.e. “target, image and treat” already observed in the preclinical studies, and has demonstrated a clinical benefit for the majority of patients in this study.

NANORAD 1 was published twice :
– NH TherAguix and the CHU Grenoble-Alpes announce the publication of the results of the First-In-Human phase 1 clinical trial
– Theranostic AGuIX nanoparticles as radiosensitizer: A phase I, dose-escalation study in patients with multiple brain metastases (NANO-RAD trial)

5 ongoing clinical trials about cancer in Europe and the US

– NANORAD 2, a multicenter Phase 2 trial, which is a continuation of the NANORAD 1 trial for the treatment of brain metastases, involving 100 patients. This trial is funded by NH TherAguix and promoted by the Grenoble University Hospital;

– NANOCOL, a Phase 1b trial in combination with cisplatin-based chemo-radiotherapy followed by brachytherapy (a radiotherapy technique that consists of placing radioactive elements inside the body, either in contact with the tumor or in the tumor itself), for the treatment of locally advanced cervical cancer – financed by a hospital-based clinical research program (PHRC) and promoted by the Gustave Roussy Institute;

– NANOBRAINMETS, a Phase 2 trial evaluating AGuIX® for the treatment of brain metastases by stereotactic irradiation. This trial is funded by NH TherAguix and promoted by the Dana Farber Cancer Institute (Harvard Medical School).

– NANOSMART, a Phase 1b/2 trial involving 100 patients to evaluate AGuIX in combination with stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) for the treatment of locally advanced or unresectable pancreatic cancers and centrally located lung cancers/metastasis. This trial is funded by NH TherAguix and sponsored by the Dana-Farber Cancer Institute (Harvard Medical School);

 – NANOGBM, a Phase 1b/2 multicentric trial involving 66 patients for the treatment of newly diagnosed glioblastoma. This trial is funded by a PHRC and sponsored by the Centre Jean Perrin (Clermont Ferrand);

Indications	Protocol	Location	Preclinical	Clinical Stage
				Phase 1	Phase 2	Phase 3
Brain Metastases	NANORAD 2 CHU Grenoble-Alpes 100 patients randomized		Recruiting Phase 2
	NANOBRAINMETS Dr. Aizer at Dana-Farber/Harvard Cancer Center 134 patients randomized		Recruiting Phase 2
Cervical Cancer	NANOCOL Institut Gustave Roussy 12 patients		Recruitment completed
Pancreatic/ Lung Cancer	NANOSMART Dr. Leeman at Dana-Farber/Harvard Cancer Center 100 patients randomized		Recruiting Phase 1
Glioblastoma	NANO-GBM Centre Jean Perrin 66 patients randomized		Recruiting Phase 1

An industrial partnership with leading partners

Internationally renowned drug manufacturers and contract research organizations (such as Sanofi, EuroAPI, Sai Life Science, Carbogen Amcis, Quality Assistance and Eurofins) are involved in the production, the characterization, and the release of AGuIX, including starting materials, and its labeling, packaging and distribution to clinical centers.