On February 20, 2019 Torque, a clinical-stage immuno-oncology company developing first-in-class Deep Primed T Cell Therapeutics to direct immune power deep within the tumor microenvironment, reported that it has entered into a clinical trial collaboration agreement with Merck (known as MSD outside of the U.S. and Canada) (Press release, Torque Therapeutics, FEB 20, 2019, View Source [SID1234553880]). The collaboration will evaluate Torque’s Deep IL-15 Primed T Cells (TRQ-1501) both as a single agent and in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in a Phase 1/2 study in multiple solid tumor indications.

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"We are very excited about this clinical collaboration with Merck to evaluate the combination of KEYTRUDA with our Deep IL-15 Primed T cells," said Bart Henderson, Chief Executive Officer of Torque. "Torque’s new class of cellular immunotherapy is designed to harness the full biology of natural T cells for treating multiple solid tumors, and we believe the combination with anti-PD-1 therapy will further enhance the function of these cells by protecting them against immunosuppression in the tumor microenvironment. This combination has the potential to improve treatment outcomes for patients with solid tumors that are relapsed or refractory to currently available treatments and broaden the applications of cellular immunotherapy."

The Phase 1/2 trial will evaluate the safety, tolerability, immune biomarkers, and overall response rates achieved with TRQ-1501 in combination with KEYTRUDA in two groups of patients:

Patients with melanoma, non-small cell lung cancer, bladder cancer, renal cell carcinoma, and head and neck cancer who are relapsed or refractory to checkpoint inhibitor therapy (anti PD-1/PD-L1 inhibitor treatment)
Patients with advanced or metastatic ovarian cancer or sarcoma who are relapsed or refractory to standard-of-care treatments
Torque will conduct the trial at multiple clinical sites in the U.S. and expects to commence the combination arm of the study with KEYTRUDA later this year.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ USA.

About TRQ-1501
Torque is developing a new class of Deep-Primed cellular immunotherapy designed to overcome the key challenges limiting broad use of cellular therapy in oncology, including the capability to target tumors that express multiple heterogeneous antigens, the ability to overcome the immunosuppressive microenvironment that shuts down T cell function, and the need for outpatient treatment with a high margin of safety. Torque uses its Deep-Priming technology to develop multi-targeted, antigen-primed T cells that carry surface-anchored immune-stimulatory drugs to drive a full immune response within the tumor microenvironment against tumors with heterogenous antigens. TRQ-1501 is an investigational immune cell therapy produced from a patient’s own T cells, which are primed to be active against multiple tumor-associated antigens and loaded with Deep IL-15 (a multimer of IL-15 cytokine) anchored to the T cells’ surface.

About Torque’s Deep-Primed Immune Cell Therapy Platform
Torque’s Deep-Priming platform uses advanced cell process engineering to:

prime and activate T cells to target multiple tumor antigens and
tether immune-stimulatory drugs to the surface of these multi-target T cells to direct immune activation in the tumor microenvironment
using a proprietary technology platform, without genetic engineering, for a high margin of safety.
Deep-Primed T cells both target multiple tumor antigens and pharmacologically activate an immune response with anchored cytokines. This process does not require genetic engineering of the T cells and so preserves the natural T cell receptor for delivering a regulated immune response, with the potential for a high margin of safety. In addition to antigen priming, immunomodulators are tethered to the surface of Deep-Primed T cells—initially IL-15 and IL-12 cytokines, and TLR agonists—that activate both innate and adaptive immunity. Administering these immunomodulators systemically to a patient can cause lethal toxicity by activating immune cells throughout the body. By loading precise doses of cytokines onto the surface of T cells, Deep Priming focuses the immune response to target the tumor, without systemic exposure.

In hematologic cancers, this new class of immune cell therapeutics has the potential to improve on the initial success of single-target CAR T therapeutics with expanded efficacy and also move cell therapy treatment out of the hospital with a high margin of safety. For solid tumors, Deep-Primed T cells have the potential to enable efficacy against tumors with heterogeneous antigens protected by hostile microenvironments, which are not readily addressable with the first generation of immune cell therapies.

On February 20, 2019 Sapreme Technologies, a privately-held biotech company developing a technology platform to enable the cytosolic delivery of macromolecule therapeutics, reported that it has been awarded a 6.8 M€ grant together with a multidisciplinary consortium including 11 other academic and industrial parties (Press release, Sapreme Technologies, FEB 20, 2019, View Source com/201902201890/sapremetechnologies-in-a-6-8-m-eu-alliance-to-develop-an oligonucleotide-delivery-platform-based-on-its-proprietary-endosomal-escape-enhancers.html [SID1234538878]). The grant was provided by the European Union (EU) through Horizon 2020 to develop a non-viral based gene therapy using Sapreme’s proprietary endosomal escape enhancers.

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Ruben Postel, CSO of Sapreme Technologies, "We are pleased to see that the EU has recognized the great potential of the ENDOSCAPE project and the expert multi-disciplinary consortium developing a novel oligonucleotide delivery technology for treatment of cancer and haemophilia patients"

Ernst Geutjes, acting Managing Director, "The fact that the EU awarded the proposal with the maximum score demonstrates the potential of Sapreme’s proprietary endosomal escape enhancement technology as well as the exceptional quality of the proposal and the consortium spearheaded by Sapreme and Charité – Universitätsmedizin Berlin"

On February 20, 2019 DelMar Pharmaceuticals, Inc. (Nasdaq: DMPI) ("DelMar" or the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported that its Phase 2 study testing VAL-083 in patients with newly diagnosed glioblastoma multiforme (GBM) has achieved its halfway enrollment point (Press release, DelMar Pharmaceuticals, FEB 20, 2019, View Source [SID1234533467]). This trial, targeted to enroll up to thirty patients, is a single-arm, open-label study testing VAL-083 in combination with standard radiotherapy in GBM patients who have an unmethylated promoter of the methylguanine DNA-methyltransferase (MGMT) gene. An estimated 60% of GBM patients possess an unmethylated MGMT gene, which confers a more limited response to current standard of care treatment as well as a lower survival probability. This clinical trial was initiated in February 2017 and is being conducted at the Sun Yat-sen University Cancer Center (SYSUCC) in Guangzhou, China in collaboration with Guangxi Wuzhou Pharmaceutical Company.

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The Company is pleased to report that for the 15 patients enrolled to date, 11 have completed their prospectively planned Magnetic Resonance Imaging (MRI) scans and have had their initial assessment for tumor progression. Tumor progression is based on the trial investigator’s clinical and radiologic assessment, according to the Response Assessment in NeuroOncology (RANO) criteria. Of these 11 patients, five were assessed by the Principal Investigator as having a "Complete Response", three of whom were based on significant tumor shrinkage, and two of whom were based on their tumors continuing to remain "below measurable level" from post-surgery baseline MRI to post-cycle 3 MRI. Additionally, six patients were assessed as having "Stable Disease." Of the remaining four patients, one died prior to their post-cycle 3 MRI and three have not been on study long enough to reach their planned post-cycle 3 MRI. As of the February 14, 2019 data cutoff, 12 of the 15 enrolled patients are still alive. Similar to prior experience, myelosuppression has been the most common adverse event observed. Two dose-limiting toxicities have been reported (thrombocytopenia) – one at the 40 mg/m2/day dose and one at the 30 mg/m2/day dose.

"GBM is a cancer with a very high unmet medical need, especially for patients with an MGMT-unmethylated biomarker who are provided with limited existing treatment options," stated Saiid Zarrabian, President and Chief Executive Officer of DelMar Pharmaceuticals. "We are encouraged that we have completed the dose escalation stage of this study and that 30 mg/m2/day of VAL-083 in combination with radiation therapy was generally safe and well-tolerated in this trial. And while these results are preliminary, we are also enthusiastic that five of the first twelve patients available for efficacy measurements have initially been assessed as having a Complete Response. With the clinical trial rapidly enrolling into its expansion phase, we look forward to providing a final data update once the study is completed."

The Company will be providing further details and an update on this trial at the annual meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) being held March 29 to April 3, 2019.

Professor Zhong-ping Chen, Founder Chairman of the Department of Neurosurgery/Neuro-oncology at Sun Yat-sen University Cancer Center, and who is also the study’s Principal Investigator, stated that "treating glioblastoma patients with an unmethylated MGMT promoter is particularly challenging. While the clinical trial is still early, and we are only at the halfway point in enrollment, we are highly encouraged at the enhanced levels of tumor shrinkage and the complete responses we are observing after treatment with VAL-083 in combination with radiation. This preliminary data appears to support the premise that VAL-083 has the potential to provide a valuable treatment option for these patients."

The clinical trial in newly diagnosed GBM is designed to enroll up to 30 patients to determine if first-line treatment with VAL-083 plus radiotherapy can provide improvements over the historical efficacy of standard of care temozolomide (TMZ) plus radiotherapy. Efficacy will be measured based on tumor response to treatment, progression-free survival, progression-free survival at six months, and overall survival compared to historical results in the target population.

The clinical trial consists of two parts:

Part 1 is a dose-escalation and induction format to confirm the recommended dose of VAL-083 when administered concurrently with radiation therapy based on safety and tolerability. The patients received VAL-083 at 20 mg/m2/day, 30 mg/m2/day or 40 mg/m2/day along with standard radiation treatment. The dose escalation phase of the study was concluded in October 2018.
Part 2 comprises an expansion phase whereby VAL-083 will be studied in up to 20 additional patients. Based on the best balance of efficacy and tolerability, the dose of VAL-083 chosen for the expansion phase of the study was 30 mg/m2/day. This phase of the study is ongoing and is continuing to enroll patients.
This phase 2 clinical trial (ClinicalTrials.gov Identifier: NCT03050736) is expected to provide the scientific basis for larger studies to support submission of marketing applications. Ideally, data from these larger studies will result in approval of VAL-083 as first line therapy for all newly-diagnosed patients with an unmethylated MGMT gene promoter.

About VAL-083

VAL-083 (Dianhydrogalactitol) is a novel bi-functional DNA targeting agent that rapidly induces interstrand cross-links at N7-guanine, leading to DNA double-strand breaks and ultimately cell death. VAL-083’s unique cytotoxic mechanism circumvents MGMT mediated chemoresistance and differentiates it from other therapies used in the treatment of GBM, including TMZ. This makes VAL-083 an ideal candidate to explore treating patients who are unlikely to respond to TMZ due to MGMT expression in their GBM as per the 2017 National Comprehensive Cancer Network guidelines.

VAL-083 has been granted orphan drug designations by the U.S. FDA Office of Orphan Products for the treatment of glioma, medulloblastoma and ovarian cancer, and in Europe for the treatment of malignant gliomas. VAL-083 has been granted fast-track status for the treatment of recurrent GBM by the US FDA.

On February 20, 2019 AOP Orphan Pharmaceuticals AG (AOP Orphan), a European pioneer in rare disease, reported that the European Commission (EC) has granted Marketing Authorization for BESREMi (Ropeginterferon alfa-2b) as first line monotherapy in adults for the treatment of Polycythaemia Vera (PV) without symptomatic splenomegaly (Press release, AOP Orphan Pharmaceuticals, FEB 20, 2019, View Source [SID1234533522]).

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BESREMi is now approved for use in all twenty-eight-member states of the European Union, as well as in Iceland, Liechtenstein and Norway.

The EC approval was based on data generated in the clinical development program, comprising of pivotal PROUD-PV, PEN-PV, PEGINVERA and the ongoing trial CONTINUATION-PV. Clinical study data on patients receiving treatment up to seven years are available underlining the long experience with BESREMi in PV.

"BESREMi is the first approved interferon in PV and now, our next goal is to make it available to patients living with this condition in Europe as soon as possible," said Andreas Steiner, Chief Executive Officer of AOP Orphan.

About BESREMi

BESREMi is a novel, long-acting, mono-pegylated proline interferon (ATC L03AB15). Its pharmacokinetic properties offer a new level of tolerability. BESREMi is designed to be self-administered subcutaneously with a pen once every two weeks, or monthly during long-term maintenance. This treatment schedule is expected to lead to overall better safety, tolerability and adherence compared to conventional pegylated interferons.

For the EC Summary of Product Characteristics please visit:

View Source

Ropeginterferon alfa-2b was discovered by PharmaEssentia Corp. based in Taiwan (see www.pharmaessentia.com). In 2009, AOP Orphan and PharmaEssentia entered into a License and Manufacturing agreement for Ropeginterferon alfa-2b which is manufactured by PharmaEssentia in its new Taichung Plant opened in Oct 2012 which has also received a GMP-certificate by a European regulatory body in Jan 2018. The finished product was developed as a pre-filled pen by Vetter (Germany) and Ypsomed (Switzerland) under the overall project lead of AOP Orphan in order to make administration easier compared to a vial or syringe. AOP Orphan has the exclusive rights for clinical development and commercialization of Ropeginterferon alfa-2b in PV, other myeloproliferative neoplasia (MPN) and chronic myeloid leukemia (CML) for European, Commonwealth of Independent States (CIS), and Middle Eastern markets. AOP Orphan informs separately when BESREMi will be available on the respective markets.

About Polycythemia Vera
Polycythemia Vera (PV) is a rare cancer of the blood-building stem cells in the bone marrow resulting in a chronic increase of red blood cells, white blood cells and platelets. This condition increases the risk for circulatory disorders such as thrombosis and embolism, its symptoms lead to a reduced quality of life and on the long run may progress to myelofibrosis or transform to leukemia. While the molecular mechanism underlying PV is still subject of intense research, current results point to blood-building stem cells in the bone marrow with a set of acquired mutations, the most important being a mutant form of JAK2 that make up the malignant clone. Important PV treatment goals are to achieve healthy blood counts (hematocrit below 45%), improve quality of life and to slow or delay the progression of disease.

On February 20, 2019 Synlogic(Nasdaq:SYBX) reported that Aoife Brennan, M.B., B.Ch., Synlogic’s president and chief executive officer, will provide a corporate update at the SVB Leerink 8th Annual Global Healthcare Conference at 1:30 pm ET on Thursday, February 28, 2019, in New York City (Press release, Synlogic, FEB 20, 2019, View Source [SID1234533486]).

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A live webcast of the presentation can be accessed under "Event Calendar" in the Investors & Media section of the Company’s website. An archive copy of the webcast will be available on the Synlogic website for approximately 30 days after the event.