about PharmaEngine
- PEP503 (crystalline hafnium oxide, NBTXR3)
There are several treatment modalities for cancer including surgery, radiation therapy, drugs, and others, depending on the site of the tumor, stage of the cancer, and the physical condition of the patients. About 50% of cancer patients receive radiotherapy around the world. Radiation therapy causes breaks to the double helix of DNA using a high energy beam, which may induce cell death. However, radiation therapy also has notable disadvantages, such as a longer treatment period and unavoidable side effects. Over the past decades, many technologies and methods have been developed to address this, and while they ameliorate some of the drawbacks of traditional radiation therapy, there is much need for further improvement.
In August 2012, PharmaEngine, Inc. and Nanobiotix, S.A. entered into a License and Collaboration Agreement on a nanoparticle radioenhancer, NBTXR3 (PEP503). In the preclinical studies, PEP503 was shown to enhance the tumor killing capability of radiation therapy, while spare the damaging side effects to the healthy tissues. PEP503 is currently undergoing a phase I clinical study in soft tissue sarcoma in France.
Thus, PEP503 should play an important role in radiation oncology therapy to remedy the disadvantage of current radiation therapy.
About PEP503 (NBTXR3)
Radiation therapy uses ionizing radiation to generate free radicals and ROS (reactive oxygen species) when it is directed toward the tumor and interacts with water molecules. The free radicals and ROS can then further break the DNA and lead to cell apoptosis.
PEP503 is a nanoparticle formulation of hafnium oxide crystals (HfO2), a radio-enhancer for local treatment. Hafnium oxide represents a high electron density nanomaterial designed to interact with ionizing radiation in order to locally (i.e. where the nanoparticles are) generate energy dose deposit. 
When PEP503 is in the tumor cell, due to the high density and atomic number of hafnium, the probability of energy absorption is higher than it of water molecular. Therefore, PEP503 will generate the same type of effect as water molecules in tumor cell under radiotherapy, but by several orders of magnitude higher. 
Clinical development
PEP503 (NBTXR3) has been designated as a class III medical device by some EU regulatory authorities. Unlike the three clinical phases required for drug approval, the regulatory approval of a medical device requires only the pilot and pivotal studies. In September 2011, PEP503 was granted approval by ANSM, the French regulatory authority (formerly AFSSAPS), to start the phase I clinical trial. A total of 22 patients were recruited in this soft tissue sarcoma study. The first preliminary clinical results were presented at the ASCO annual meeting in May 2015 and the final results were presented at ESTRO in April 2015. With the proof of concept data from the phase I trial, a pivotal study of soft tissue sarcoma was launched in Europe, South Africa, and several Asia Pacific countries. Also, Nanobiotix is conducting a phase I trial in head and neck cancer, and another phase I trial in liver cancer.
Under the license and collaboration agreement, PharmaEngine is responsible for the clinical development in the Asia Pacific region. In Taiwan, a phase Ib/II in rectal cancer is ongoing. With a comprehensive clinical development plan in place, we believe that the clinical applications of PEP503 in different indications can be accelerated.
Market potential
Nowadays about 50% of cancer patients worldwide receive radiation treatment. In Asia, potential indications for PEP503 include head and neck cancer, oral cavity cancer, rectal cancer, esophageal cancer, brain cancer and hepatocellular carcinoma,.  There is a niche role for PEP503 in this huge radiotherapy market.
* S. Bonvalot, C.L. Pechoux, T.D. Baere, et al; Phase I study of NBTXR3 nanoparticles, in patients with advanced soft tissue sarcoma (STS). J Clin Oncol 32:5s, 2014 (suppl; abstr 10563)
* Marill J, Anesary NM, Zhang P, Vivet S, Borghi E, Levy L, Pottier A. Hafnium oxide nanoparticles: toward an in vitro predictive biological effect? Radiat Oncol. 2014 Jun 30;9:150.
* Pottier A, Borghi E, Levy L. New use of metals as nanosized radioenhancers. Anticancer Res. 2014 Jan;34(1):443-53. Review.