PharmaEngine Announces Positive Topline Results from Global Pivotal Trial of PEP503 (NBTXR3) in Soft Tissue Sarcoma

Taipei, Taiwan, June 21, 2018

PharmaEngine Inc. (TWO: 4162) and its corporate partner, Nanobiotix S.A. (Euronext: NANO) announced today that PEP503 (NBTXR3) in combination with radiotherapy met the primary endpoint of pathological Complete Response Rate (pCRR) as compared to radiotherapy alone in a global pivotal phase II/III trial in patients with locally advanced soft tissue sarcoma (STS) of the extremity and trunk wall. The pCRR on the combination arm was 16.1% as compared to 7.9% for the control arm of radiotherapy alone (p = 0.0448). Also PEP503 activated by radiation demonstrated a significant increase of R0 resection rate as compared to radiation alone (p = 0.042). PEP503 demonstrated a good local tolerance among this patient population. The findings showed a very similar radiation-related safety profile in both arms.

This prospectively randomized, multi-national, open-label and active controlled two-arm (1:1 ratio) pivotal phase II/III trial, referred to as Study 301 (act.in.sarc study) has been conducted in partnership with Nanobiotix. PharmaEngine is the co-sponsor of this study in Asia-Pacific Region. The antitumor activity and safety of PEP503 combined with radiotherapy in Study 301 was compared with that of radiotherapy alone, as preoperative treatment. The primary objective of Study 301 is to enhance pCRR by dosing PEP503 through intra-tumor injection and then activated by standard dose (25 x 2 Gy) of external beam radiation therapy (EBRT). The secondary endpoints are the objective response rate (ORR) by imaging (MRI); the tumor volume changes; the resection margins (R0 rate) and the limb amputation rate, as well as the evaluation of the safety profile in term of clinical and laboratory adverse events. The detailed data analysis, with the exception of long-term follow up will be reported in an international medical conference in the next few months.

“We are very pleased to take part in the global study alongside with Nanobiotix, and are excited that PEP503 has achieved the primary and secondary endpoints of this pivotal study in STS patients.”

The promising results from this study validated its fundamental mechanism of action as a radio-enhancer, which is expected to be generally applicable in other cancers treated with radiotherapy. In addition, previously reported preliminary data from a small set of tumor samples in this study demonstrated that PEP503 activated by radiotherapy induces a specific adaptive immune pattern as an immune-enhancer, while radiotherapy alone did not show any impact on triggering adaptive immune response.”

C. Grace Yeh, Ph.D., President and CEO of PharmaEngine

ABOUT STUDY 301 (ACT.IN.SARC STUDY)

The Study 301 recruited a total of 180 patients in Europe (36 sites in 10 countries) by Nanobiotix, and in Asia-Pacificregion (7 sites in Australia, Hong Kong, and Philippines) by PharmaEngine. The Global Principal Investigator is Dr. Sylvie Bonvalot, MD, PhD (Head of Sarcoma and Complex Tumor Surgery Unit, Institut Curie, Paris, France). The primary endpoint of pCRR is defined as the rate of patients showing less than 5% of residual viable cancer cells in the tumor post treatment. A centralized evaluation of the pathological response was performed. For additional information, please visit www.clinicaltrials.gov (Identifier: NCT02379845) or learn more on the www.actinsarc.com study website (both linked below).

clinicaltrials.gov
actinsarc.com
ABOUT PEP503 (NBTXR3)

NBTXR3, the lead project of the NanoXray pipeline of Nanobiotix, is a nanoparticle formulation of hafnium oxide crystals for the local treatment of tumors to enhance the efficacy of radiotherapy. In August 2012, PharmaEngine licensed the development and commercialization rights of NBTXR3 in the Asia-Pacific region from Nanobiotix.In 2014, Nanobiotix presented the pilot study results for NBTXR3 in patients with soft tissue sarcomas at ASCO, which showed a good safety profile and positive signs of efficacy. Then the preliminary pilot studyresults in head and neck cancerpatients (without receiving chemotherapy) and liver cancer patients presented at ASCO 2017and ASCO GI 2018,respectively, also showedpromisingsigns of anti-tumoreffect.

There are other indications being developed for NBTXR3 by Nanobiotix and PharmaEngine. These includehead and neck cancer in patients receiving chemotherapy (Phase I/II, PharmaEngine), rectal cancer (Phase I/II, PharmaEngine), liver cancer (Phase I/II, Nanobiotix)andprostate cancer (Phase I/II, Nanobiotix). NBTXR3 has been classified as a class III medical device in many European and certain Asian countries. Learn more here.

ABOUT SOFT TISSUE SARCOMA (STS)

STS are rare malignant tumors that arise from extraskeletal connective tissues, accounting for 0.7% of all cancers. They can occur anywhere in the body, but most originate in an extremity and the trunk (78%). The conventional treatment for STS is wide margin surgery whenever possible with the addition of radiotherapy. In locally advanced STS, however, clear margins are not often achievable, which could lead to higher local failure rates, and negatively affect overall survival. Scientific reports have demonstrated how preoperative radiotherapy can offset the negative prognostic impact of marginal resection on local outcome and survival for patients with STS, extending the limit of limb and function preservation.

Although improvements in surgical techniques and preoperative radiotherapy have been made, local tumor recurrence and distant metastases have been frequently noted to develop. PEP503 (NBTXR3), a radio-enhancer designed to maximize x-ray absorption within the tumor, aims to improve the efficacy of radiotherapy and increase the feasibility of surgical tumor removal.

ABOUT PHARMAENGINE

PharmaEngine, Inc. (TWO: 4162) is a commercial stage oncology company headquartered in Taipei, Taiwan with a wholly owned subsidiary, PharmaEngine Europe Sarl in Paris, France. PharmaEngine focuses on the development of new medications for the treatment of cancer and Asian prevalent diseases. PharmaEngine has three ongoing projects: ONIVYDE® (Irinotecan Liposome Injection) has received marketing authorizations in Taiwan, US, Europe and other countries for the treatment of metastatic pancreatic cancer patients who progressed on gemcitabine; PEP503 (NBTXR3) in a global pivotal trial of soft tissue sarcoma and in other cancers; and PEP06 in preclinical development. Get to know more here.

Contact

Chihsing Chang, Vice President, Finance and Administration
P +886 2 2515 8228, ext. 700
chihsing.chang@pharmaengine.com