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Moleculin Announces the FDA has Granted Orphan Drug Designation for its Brain Tumor Drug

On February 5, 2019 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company focused on the development of oncology drug candidates, all of which are based on license agreements with The University of Texas System on behalf of the M.D. Anderson Cancer Center, reported that the US Food and Drug Administration (FDA) has granted Orphan Drug Status for its drug candidate WP1066 for the treatment of glioblastoma, the most aggressive form of brain tumor (Press release, Moleculin, FEB 5, 2019, View Source [SID1234533053]).

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"We continue to be encouraged by the progress of the physician-led clinical trial of WP1066," commented Walter Klemp, Moleculin’s Chairman and CEO, "and, now having the FDA grant Orphan Drug status for WP1066 positions us well for potential marketing of this drug. We believe that WP1066 represents a new class of drugs which we call ‘Immune/Transduction Modulators’ because it has demonstrated the ability in preclinical testing in animals to both stimulate a natural immune response to tumors and directly attack tumor cells by inhibiting multiple key oncogenic transcription factors, including STAT3, HIF1-α and c-Myc."

Dr. Sandra Silberman, Chief Medical Officer for New Projects at Moleculin added: "The development of WP1066 is gaining momentum. In addition to the glioblastoma trial at MD Anderson, we have had interest from additional investigators, including Emory University and Mayo Clinic for conducting clinical trials for the treatment of pediatric brain tumors, as well as others interested in treating a range of highly resistant tumors including AML and pancreatic cancer. Because we’ve seen strong anti-tumor activity in a wide range of animal models, we believe this represents an important new approach to treating many types of cancer."

The FDA grants orphan drug designation to drugs and biologics that are intended for the treatment of rare diseases that affect fewer than 200,000 people in the U.S. Orphan drug status is intended to facilitate drug development for rare diseases and may provide several benefits to drug developers, including tax credits for qualified clinical trials costs, exemptions from certain FDA application fees, and seven years of market exclusivity upon regulatory product approval.

Roche submits supplemental biologics license application to the US FDA for Kadcyla for adjuvant treatment of people with HER2-positive early breast cancer with residual disease after neoadjuvant treatment

On February 5, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported completing the submission of a supplemental Biologics License Application to the US Food and Drug Administration (FDA) for Kadcyla (trastuzumab emtansine) for adjuvant (after surgery) treatment of people with HER2-positive early breast cancer (eBC) with residual disease after neoadjuvant (before surgery) treatment (Press release, Hoffmann-La Roche, FEB 5, 2019, View Source [SID1234533047]). The FDA is reviewing the application under the Real-Time Oncology Review and Assessment Aid pilot programmes, which aim to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible.[1,2] For this indication, Kadcyla was also granted Breakthrough Therapy Designation, which is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases.[3]

"Kadcyla was granted Breakthrough Therapy Designation and is also the first Roche medicine to be reviewed under the FDA’s Real-Time Oncology Review pilot programme; both FDA initiatives aim to expedite reviews and bring medicines to patients sooner" said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "We are working closely with the FDA to bring Kadcyla to people with HER2-positive early breast cancer who have residual disease after neoadjuvant therapy as early as possible."

This application is based on results of the phase III KATHERINE study showing Kadcyla significantly reduced the risk of invasive breast cancer recurrence or death from any cause (invasive disease-free survival; iDFS) by 50% (HR=0.50, 95% CI 0.39-0.64, p<0.0001) compared to Herceptin (trastuzumab) as an adjuvant treatment in people with HER2-positive eBC who have residual disease present following neoadjuvant treatment.[4] People who have residual disease after neoadjuvant treatment have a worse prognosis than those with no detectable disease. At three years, 88.3% of people treated with Kadcyla did not have their breast cancer return compared to 77.0% treated with Herceptin, an absolute improvement of 11.3%.[4]

The most common Grade 3-4 side effects (>1%) with Kadcyla in the KATHERINE study were decreased platelet count; high blood pressure; radiation-induced skin injury; numbness, tingling or pain in the hands or feet; decreased neutrophil count; low blood potassium level; fatigue and decrease in red blood cells.[4]

About the KATHERINE study[5]
KATHERINE is an international, multi-centre, two-arm, randomised, open-label, phase III study evaluating the efficacy and safety of Kadcyla versus Herceptin as an adjuvant therapy in people with HER2-positive eBC who have pathological invasive residual disease in the breast and/or axillary lymph nodes following neoadjuvant therapy that included Herceptin and taxane-based chemotherapy. The primary endpoint of the study is iDFS, which in this study is defined as the time from randomisation free from invasive breast cancer recurrence or death from any cause. Secondary endpoints include disease-free survival and overall survival.

About Kadcyla
Kadcyla is an antibody-drug conjugate (ADC) engineered to deliver potent chemotherapy directly to HER2-positive cancer cells, potentially limiting damage to healthy tissues.[6,7] It combines two anti-cancer properties joined together by a stable linker: the HER2-targeting properties of trastuzumab (the active ingredient in Herceptin) and the chemotherapy agent DM1.[8] Kadcyla is the only ADC approved as a single agent in 104 countries including the US and EU for the treatment of people with HER2-positive metastatic breast cancer who have previously received Herceptin and taxane chemotherapy, separately or in combination. Roche licenses technology for Kadcyla under an agreement with ImmunoGen, Inc.

About Roche’s medicines for HER2-positive breast cancer
Roche has been leading research into the HER2 pathway for over 30 years and is committed to improving the health, quality of life and survival of people with both early and advanced HER2-positive disease. HER2-positive breast cancer is a particularly aggressive form of the disease that affects approximately 15-20% of patients.[9] Roche has developed three innovative medicines that have helped transform the treatment of HER2-positive breast cancer: Herceptin (trastuzumab), Perjeta (pertuzumab) and Kadcyla (trastuzumab emtansine). Eligibility for treatment with Roche’s HER2-targeted medicines is determined via a diagnostic test, which identifies people who will likely benefit from these medicines at the onset of their disease.

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.

"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]).

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.

"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.