ENB Therapeutics Announces Clinical Trial Collaboration with Merck to Evaluate ENB-003 in combination with KEYTRUDA® (pembrolizumab) for Advanced Solid Tumors

On February 4th, 2019 ENB Therapeutics, Inc., a clinical-stage, biopharmaceutical company developing innovative, endothelin-based oncologics, reported that it has entered into a clinical collaboration agreement with Merck (known as MSD outside the U.S. and Canada) to evaluate the combination of ENB-003, a first-in class endothelin B receptor ("ETBR") inhibitor and Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in a Phase 1/2 trial in patients with advanced solid tumors (Press release, ENB Therapeutics, FEB 4, 2019, View Source [SID1234626430]). The open-label, dose-escalation and expansion Phase 1/2 study will enroll patients with anti-PD-1 resistant malignant melanoma, platinum-resistant ovarian or pancreatic cancer with previous treatment failure. The dose escalation phase of the trial will evaluate the safety and tolerability of various doses of ENB-003 as a monotherapy and in combination with KEYTRUDA. The dose expansion will evaluate preliminary efficacy, safety and tolerability of the selected dose of ENB-003 combined with KEYTRUDA as well as changes in immunohistochemistry and pharmacodynamic biomarkers after administration of ENB-003.

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"We are thrilled to collaborate with Merck, an established leader in the field of cancer immunotherapy," said Sumayah Jamal, M.D., Ph.D., President and CSO of ENB Therapeutics. "ENB-003 has both antitumor and immune-modulatory effects and augments the efficacy of anti-PD-1 inhibition in animal models. We are optimistic about exploring the combination of ENB-003 and KEYTRUDA ."

Under the terms of the agreement, ENB Therapeutics will sponsor the ENB-003 and KEYTRUDA clinical study.

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

Torque and Thermo Fisher Scientific Announce Collaboration to Build State-of-the-Art Facility to Manufacture Torque’s Deep-Primed T Cell Immunotherapies

On February 4, 2019 Torque, an immuno-oncology company developing first-in-class Deep Primed T Cell Therapeutics to direct immune power deep within the tumor microenvironment, and Thermo Fisher Scientific Inc. (NYSE: TMO), reported a collaboration to build a dedicated Slipstream manufacturing facility for high-efficiency production of Torque’s Deep-Primed T cell immunotherapies (Press release, Torque Therapeutics, FEB 4, 2019, View Source [SID1234553883]).

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Buildout of the Torque/Thermo Fisher manufacturing facility has begun, and the companies anticipate processing patient cells by the end of 2019. The Slipstream platform will initially be used in the clinical development of Torque’s lead Deep-Primed T cell candidate, TRQ-1501, in solid and hematologic tumors; followed by TRQ-1201, also for solid and hematologic tumors.

"Torque’s cell manufacturing technology platform is critical to achieving our goal of developing and commercializing a new class of cellular immunotherapy for cancer patients with both early and advanced disease, particularly for the large population of solid tumor patients in need of new treatments," said Bart Henderson, CEO of Torque. "We are very excited about partnering with Thermo Fisher to build this state-of-the-art manufacturing facility because of their vision and exceptional track record in building high-efficiency, globally integrated operations. This is a pioneering manufacturing partnership with the goal of dramatically improving the efficiency and scalability of producing best-in-class cellular immunotherapy products that have the potential to benefit a significant number of cancer patients."

"Thermo Fisher is dedicated to advancing precision medicine, and our collaboration with Torque is a tangible example of the progress we are making to become a recognized leader in cell therapy manufacturing," said Michel Lagarde, President of Pharma Services for Thermo Fisher Scientific. "We are pleased to partner with Torque to build and launch this unique and advanced manufacturing facility utilizing the Slipstream technology, Torque’s innovative cellular immunotherapy product, which has the potential to transform cancer treatment and patients’ lives."

The Slipstream platform technology situated in Princeton is a revolutionary design that uses a fully closed, semi-automated system that surpasses conventional cell therapy manufacturing techniques. The Slipstream process leverages advanced logistics that enable a substantially smaller manufacturing footprint that is less capital- and labor-intensive. Production capacity can be expanded modularly by adding arrays in Lego-like fashion.

About Slipstream Cell Therapy Manufacturing Technology
Slipstream is a proprietary, high-efficiency T cell manufacturing platform engineered by Torque. Currently marketed immune cell therapies are produced using open, complex, labor- and cost-intensive processes that require a substantial manufacturing facility. In contrast, Slipstream production is semi-automated and fully closed, which eliminates contamination risk between transfers and can dramatically reduce staffing requirements and the factory footprint. The cell engineering process uses a modular design that enables both large-scale and decentralized manufacturing. Slipstream has the potential to improve manufacturing efficiency beyond what is possible with currently used cell therapy manufacturing processes and to move cell therapy production closer to the point of care.

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.

Syntrix Wins $3.4M NIH Grant to Conduct Phase 1/2 Trial of SX-682 in Myelodysplastic Syndrome

On February 4, 2019 Syntrix Pharmaceuticals reported that it has been awarded a three-year grant worth $3.4 million from the National Heart Lung and Blood Institute of the National Institutes of Health to assess its investigational CXCR1/2 inhibitor SX-682 in patients with low- and high-risk myelodysplastic syndrome (MDS) who had progression or were intolerant to prior therapy (Press release, Syntrix, FEB 4, 2019, View Source [SID1234553882]). The phase 1/2 clinical trial will be carried out in collaboration with researchers at the Moffitt Cancer Center led by Dr. Rami Kamrokji.

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"Patients with low-risk MDS have an expected median survival measured in years, but suffer from hematologic deficits and related symptoms that lead to transfusion dependence," said Syntrix’s President John Zebala. "Patients with high-risk MDS have debilitating cytopenias and borderline leukemia, and can have expected survival measured in months."

Only three drugs have received regulatory approval for MDS treatment, all with suboptimal response rates (<50%) and of limited durability (1-2 years). Once these agents fail in patients, there is no second-line treatment. Prognosis after failure is dismal, with median survival estimated at <6 months for higher-risk patients, and <18 months for lower-risk patients.

The Phase 1/2 clinical trial of SX-682 builds on groundbreaking discoveries by investigators at the Moffitt Cancer Center and the Albert Einstein College of Medicine who showed CXCR1/2 is pivotal in MDS and that its inhibition is a therapeutic strategy against the disease.

This Phase 1/2 trial in MDS patients will test the hypothesis that targeting CXCR1/2 with SX-682 will be efficacious in the disease by eliminating the MDS stem cells and bone marrow MDSCs. The FDA approved the protocol for the study in an IND sponsored by Syntrix.

ABOUT SX-682: SX-682 is a clinical-stage oral allosteric small-molecule inhibitor of CXCR1 and CXCR2 (CXCR1/2). Inhibiting both human receptors is believed essential. CXCR1/2 are a combined "master switch" of the immunosuppressive tumor microenvironment. Clinical studies in melanoma, breast, ovarian, prostate and colon cancer have shown a direct correlation between serum levels of CXCR1/2 ligands and disease progression. SX-682 has been validated in all major solid tumor models, where it exhibits mono-agent anti-tumor activity, blocks metastasis, depletes immunosuppressive myeloid cells, activates tumor killing by effector cells, reverses chemo-resistance, and potently synergizes with anti-CTLA-4 and anti-PD1. SX-682 is also being evaluated in solid tumors supported by the National Cancer Institute.

Neurotrope Announces Cooperative Research and Development Agreement for Bryostatin-1 with the National Cancer Institute

On February 4, 2019 Neurotrope Inc. (NASDAQ:NTRP), a clinical-stage biopharmaceutical company developing novel therapies for neurodegenerative diseases, including Alzheimer’s disease (AD), reported that it has entered into a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI) for the research and clinical development of Bryostatin-1 (Press release, Neurotrope, FEB 4, 2019, View Source [SID1234553879]). Under the CRADA, Neurotrope will collaborate with the NCI’s Center for Cancer Research, Pediatric Oncology Branch (POB) to develop a Phase I clinical trial testing the safety and toxicity of Bryostatin-1 in children and young adults with CD22 + leukemia and B-cell lymphoma. In the growing era of highly effective immunotherapies targeting cell-surface antigens (e.g., CAR-T cell therapy), and the recognition that antigen modulation plays a critical role in evasion of response to immunotherapy, the ability for Bryostatin-1 to upregulate CD22 may serve a synergistic role in enhancing the response to a host of CD22 targeted therapies.

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Nirali N. Shah, M.D. of the NCI’s POB will be Principal Investigator for the study, and Daniel Alkon, M.D., President and Chief Scientific Officer of Neurotrope, will serve as Co- Principal Investigator.

"We believe that this collaboration with the NCI’s Center for Cancer Research provides further validation of the potential for Bryostatin-1 to affect disease pathways across a broad spectrum of indications," said Dr. Alkon. "In oncology, Bryostatin’s potential capability to increase CD22 expression may enhance the development of newer and more effective therapies for children and young adults suffering with CD22-positive leukemia and B-cell lymphoma. The enthusiasm for this collaboration stems from the POB’s long vested interest and experience targeting CD22, and we look forward to leveraging the expertise of Dr. Shah and her team to enhance our ongoing efforts to identify the most promising potential applications for Bryostatin-1."

Bryostatin-1 is a macrocytic lactone shown to increase CD22 expression in chronic lymphocytic leukemia. Under the CRADA, Bryostatin-1 is expected to be tested in the clinic to evaluate its ability to modulate CD22 in patients with relapsed/refractory CD22+ disease, while evaluating safety, toxicity and overall response.

"The initiation of our oncology collaboration with the NCI, coupled with the recent positive safety evaluation of our confirmatory Phase 2 AD trial, both demonstrate Bryostatin’s broad potential," stated Dr. Charles Ryan, Chief Executive Officer of Neurotrope. "We enter 2019 with strong momentum clinically as well as operationally, with the successful completion of a financing in December 2018. We expect that 2019 will be a transformational year for Neurotrope as we move toward data in our AD program in the second half of the year, and seek out additional collaborations to fully explore the platform potential of Bryostatin-1."

Neurotrope also announced today the completion of the first safety evaluation of the Company’s ongoing, placebo-controlled confirmatory Phase 2 trial evaluating Bryostatin-1 (20 µg) in 100 moderate to severe Alzheimer’s disease patients not on memantine. The study’s data safety and monitoring board found no safety concerns and recommended continuation of the trial as designed. Enrollment in the study, which was initiated in July 2018, is proceeding as planned, with data expected during the second half of 2019.

Calithera Biosciences Completes Patient Enrollment in Randomized Phase 2 ENTRATA Trial of Telaglenastat (CB-839) and Everolimus in Renal Cell Carcinoma

On February 4, 2019 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical stage biotechnology company focused on discovering and developing novel small molecule drugs directed against tumor metabolism and tumor immunology targets for the treatment of cancer, reported that it has completed patient enrollment in the ongoing Phase 2 ENTRATA trial. ENTRATA is a randomized clinical study of the glutaminase inhibitor CB-839 combined with everolimus versus placebo with everolimus for the treatment of advanced renal cell carcinoma (RCC) (Press release, Calithera Biosciences, FEB 4, 2019, View Source [SID1234535231]). CB-839 now has the International Nonproprietary Name (INN) telaglenastat, as recommended by the World Health Organization.

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"The ENTRATA trial is the first randomized trial evaluating the glutaminase inhibitor telaglenastat. There is ample evidence demonstrating the potential of glutaminase inhibition to block growth and survival of cancer cells," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera. "We are pleased that patient enrollment is now complete and look forward to learning more from ENTRATA about how this promising mechanism could help heavily pre-treated patients with advanced renal cancer."

The ENTRATA trial (NCT03163667) is a Phase 2 randomized, double blind trial designed to evaluate the safety and efficacy of telaglenastat in combination with everolimus versus placebo with everolimus in patients with advanced clear cell RCC who have been treated with at least two prior lines of systemic therapy, including a VEGFR-targeted tyrosine kinase inhibitor. The trial enrolled 69 patients at multiple centers in the United States. The primary endpoint of ENTRATA is progression-free survival (PFS). Calithera plans to report efficacy and safety data from the trial in the second half of 2019.

Telaglenastat is an investigational, novel glutaminase inhibitor specifically designed to block glutamine consumption in tumor cells. RCC tumors commonly exhibit metabolic alterations that increase their dependence on glutamine. In preclinical studies, telaglenastat produced synergistic antitumor effects when used in combination with standard-of-care RCC therapies.

Telaglenastat is also being investigated in the CANTATA trial, which will enroll approximately 400 patients and is designed with registrational intent. It is a global, randomized, double-blind trial designed to evaluate the safety and efficacy of telaglenastat in combination with cabozantinib versus placebo with cabozantinib in patients with advanced clear cell RCC who have been treated with one or two prior lines of systemic therapy. The primary endpoint is PFS by blinded independent review, and a key secondary endpoint is overall survival.