On June 21, 2018 PharmaEngine Inc. (TWO: 4162) and its corporate partner, Nanobiotix S.A. (Euronext: NANO) reported 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 (Press release, PharmaEngine, JUN 21, 2018, View Source [SID1234527423]). 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.

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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," said C. Grace Yeh, Ph.D., President and Chief Executive Officer of PharmaEngine. "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."

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-Pacific region (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).

About PEP503 (NBTXR3)

PEP503, the lead project of the NanoXray pipeline of Nanobiotix, is a nanoparticle formulation of hafnium oxide crystals. It is a first-in-class product designed to destroy, when activated by radiotherapy, tumors through physical cell death and metastasis via immunogenic cell death leading to specific activation of the immune system. In August 2012, PharmaEngine licensed the development and commercialization rights of NBTXR3 in the Asia-Pacific region from Nanobiotix. In addition to STS, Nanobiotix and PharmaEngine are performing clinical trials in head & neck cancers, liver cancers (liver metastasis and hepatocellular carcinoma), rectal cancer, prostate cancer, as well as in combination with anti-PD1 antibodies in head & neck cancers and non-small cell lung cancer. PEP503 has been classified as a class III medical device in many European and certain Asian countries.

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.

On June 21, 2018 MetaStat, Inc. (OTCQB: MTST), a precision medicine company developing novel anti-metastatic medications for patients with aggressive cancer, reported that positive results from preclinical studies showing treatment with MAPKAPK2 kinase inhibitors reverse MENA-driven aggressive tumor cell phenotypes and significantly reduce metastasis at the Cancer Dormancy and Residual Disease meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in Montreal, Quebec on June 20, 2018 (Press release, MetaStat, JUN 21, 2018, https://ir.stockpr.com/metastat/company-news/detail/399/metastat-presents-positive-data-showing-inhibition-of-the-mena-pathway-reduces-cancer-cell-dissemination-and-paclitaxel-resistance-in-aggressive-cancer [SID1234527413]).

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"Until recently, the MENA pathway was considered to be an undruggable target. These results show inhibition of the MENA pathway and reversal of MENA-dependent phenotypes are possible by targeting MAPKAPK2," stated Douglas A. Hamilton, MetaStat’s President and CEO. "We are leveraging a proven and highly successful therapeutic strategy in oncology to develop proprietary first-in-class MAPKAPK2 kinase inhibitors."

MetaStat reported MENA-induced fibronectin remodeling, tumor cell adhesion and invasion were reversed to MENA-null levels when treated with MAPKAPK2 inhibitors in vitro. MAPKAPK2 inhibitor monotherapy reduced lung metastasis similar to the previously published effects of MENA deficiency in the MMTV-PyMT murine model. Significant decreases in the number of animals with any detectable circulating tumor cells (CTCs) following treatment were reported in the MDA-MB-231 human metastatic triple negative breast cancer model. Further, in contrast to paclitaxel monotherapy, treatment with the MAPKAPK2 inhibitor alone or in combination with paclitaxel significantly reduced the growth rate of MMTV-PyMT primary tumors and the development of lung metastasis.

On June 21, 2018 Blueprint Medicines Corporation (NASDAQ: BPMC), a leader in discovering and developing targeted kinase medicines for patients with genomically defined diseases, reported it has dosed the first patient in the VOYAGER Phase 3 clinical trial, which is evaluating the safety and efficacy of avapritinib compared to regorafenib in patients with advanced gastrointestinal stromal tumors (GIST) (Press release, Blueprint Medicines, JUN 21, 2018, View Source;p=RssLanding&cat=news&id=2355440 [SID1234527414]). The VOYAGER trial is designed to enroll patients previously treated with imatinib and one or two additional tyrosine kinase inhibitors (TKIs).

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"The initiation of the VOYAGER Phase 3 trial represents an important milestone for Blueprint Medicines, as we advance efforts to achieve registration of avapritinib in a broad GIST population," said Andy Boral, M.D., Ph.D., Chief Medical Officer of Blueprint Medicines. "With compelling Phase 1 clinical data showing objective responses and prolonged progression free survival in heavily pretreated patients, we believe avapritinib has the potential to offer improved disease control to patients with third-line and later advanced GIST."

Avapritinib is a potent and selective inhibitor of activated KIT and PDGFRA mutant kinases. TKIs currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced GIST only bind to the inactive conformations of KIT and PDGFRA, whereas avapritinib is uniquely designed to bind and inhibit the active conformation of these protein kinases. This allows for potent inhibition of both primary and secondary mutations that shift the kinase towards its active conformation. In patients with relapsed metastatic GIST whose disease has progressed following treatment with imatinib, resistance mutations in the activation loop accumulate with higher frequency, limiting the effectiveness of approved TKIs.

About the VOYAGER Phase 3 Clinical Trial

The VOYAGER clinical trial is a global, open-label, randomized, Phase 3 trial designed to evaluate the safety and efficacy of avapritinib versus regorafenib in patients with third- or fourth-line advanced GIST. Eligible patients will have previously received imatinib and one or two additional tyrosine kinase inhibitors. The trial is designed to enroll approximately 460 patients randomized 1:1 to receive avapritinib dosed at 300 mg once daily (QD) or regorafenib dosed at 160 mg QD for three weeks, followed by one week off, at multiple sites in the United States, European Union, Australia and Asia. Patients who are randomized to receive regorafenib and experience disease progression confirmed by central radiology review may be offered the opportunity to cross-over to the avapritinib treatment arm. The primary efficacy endpoint is progression free survival determined by central radiologic assessment per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints include objective response rate, overall survival and quality of life outcome measures. Regorafenib, also known as Stivarga, is an oral, multi-kinase inhibitor approved by the U.S. Food and Drug Administration for the treatment of patients with third-line GIST.

Patients and physicians interested in the VOYAGER Phase 3 trial can contact the Blueprint Medicines study director at [email protected] or 1-617-714-6707. For more information about the VOYAGER trial, please visit www.voyagertrial.com. Additional details are also available on www.clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT03465722).

About Avapritinib

Avapritinib is an orally available, potent and highly selective inhibitor of KIT and PDGFRA. In certain diseases, a spectrum of clinically relevant mutations forces the KIT or PDGFRA protein kinases into an increasingly active state. Avapritinib is uniquely designed to bind and inhibit the active conformation of these proteins, including PDGFRα D842V and KIT D816V at sub-nanomolar potency. Blueprint Medicines is initially developing avapritinib, an investigational medicine, for the treatment of patients with advanced GIST and systemic mastocytosis.

In June 2017, avapritinib received Breakthrough Therapy Designation from the FDA for the treatment of patients with unresectable or metastatic GIST harboring the PDGFRα D842V mutation. Previously, the FDA granted orphan drug designation to avapritinib for GIST and mastocytosis and fast track designation to avapritinib for GIST. In addition, the European Commission has granted orphan drug designation to avapritinib for GIST. In May 2018, Blueprint Medicines announced plans to submit a New Drug Application to the FDA for avapritinib for the treatment of PDGFRα D842V-driven GIST in the first half of 2019. In June 2018, Blueprint Medicines announced an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of avapritinib and certain other drug candidates in Mainland China, Hong Kong, Macau and Taiwan.

About GIST

GIST is a sarcoma, or tumor of bone or connective tissue, of the gastrointestinal (GI) tract. Tumors arise from cells in the wall of the GI tract and occur most often in the stomach or small intestine. Most patients are diagnosed between the ages of 50-80, and diagnosis is typically triggered by GI bleeding, incidental findings during surgery or imaging and, in rare cases, tumor rupture or GI obstruction.

Most GIST cases are caused by a spectrum of clinically relevant mutations that force the KIT or PDGFRA protein kinases into an increasingly active state. In addition, resistance mutations in the activation loop accumulate with higher frequency in heavily pretreated patients. Because currently available therapies only bind to the inactive protein conformations, certain primary and secondary mutations typically lead to treatment resistance and disease progression.

Treatment options for KIT-driven GIST patients whose disease progresses or develops resistance are currently limited, with approved therapies providing a progression free survival of up to six months and a response rate between five percent and seven percent. There are no effective treatment options for patients with PDGFRα D842V-driven GIST, and progression often occurs in as little as three months with available treatment options.

On June 20, 2018 ERYTECH Pharma (Euronext Paris:ERYP) (Nasdaq:ERYP), a clinical-stage biopharmaceutical company developing innovative therapies by encapsulating therapeutic drug substances inside red blood cells, reported that Chief Executive Officer, Gil Beyen, will present at the JMP Securities Life Science Conference, June 20, 2018 at The St. Regis, New York, in New York City (Press release, ERYtech Pharma, JUN 20, 2018, View Source;p=RssLanding&cat=news&id=2355228 [SID1234527399]).

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Conference Details:

– Conference: JMP Securities Life Science Conference

– Date: June 20, 2018

– Presentation Time: 9:00 AM EDT / 3:00 CET

On June 20, 2018 Abbott (NYSE: ABT) reported that it will announce its second-quarter 2018 financial results on Wednesday, July 18, 2018, before the market opens (Press release, Abbott, JUN 20, 2018, View Source [SID1234527401]).

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The announcement will be followed by a live webcast of the earnings conference call at 8 a.m. Central time (9 a.m. Eastern), and will be accessible through Abbott’s Investor Relations website at www.abbottinvestor.com. An archived edition of the call will be available later that day.