On June 29, 2018 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion recommending marketing authorisation of Vyxeos 44 mg/100 mg powder for concentrate for solution for infusion for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukaemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) (Press release, Jazz Pharmaceuticals, JUN 29, 2018, View Source;p=RssLanding&cat=news&id=2356615 [SID1234527512]). Vyxeos is an advanced liposomal formulation that delivers a fixed-ratio (1:5) of daunorubicin and cytarabine.

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"Jazz is committed to bringing new and clinically meaningful treatment options to patients on a global basis, and we now look forward to bringing Vyxeos to adults with AML in the European Union," said Allen Yang, M.D., Ph.D., vice president, hematology/oncology therapeutic area head, and acting chief medical officer at Jazz Pharmaceuticals. "If approved by the European Commission, Vyxeos will become the first chemotherapy treatment option specifically for European patients with therapy-related AML or AML with myelodysplasia-related changes."

The Marketing Authorisation Application (MAA) for Vyxeos includes clinical data from five studies, including the pivotal Phase 3 study. Data from the Phase 3 study, which met its primary endpoint, were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June 2016.

Jazz Pharmaceuticals filed a MAA for Vyxeos in November 2017 after the CHMP granted accelerated assessment, which is designed to reduce the review timeline for products of major interest for public health and therapeutic innovation. The positive opinion from the CHMP will be reviewed by the European Commission, which has the authority to approve medicines in all European Union Member States, Iceland, Norway and Liechtenstein.

About Vyxeos
Vyxeos 44 mg/100 mg powder for concentrate for solution for infusion is an advanced liposomal formulation that delivers a fixed-ratio (1:5) of daunorubicin and cytarabine to the bone marrow that has been shown to have synergistic effects at killing leukaemia cells in vitro and in animal models. Vyxeos is the first product developed with the company’s proprietary CombiPlex platform, which enables the design and rapid evaluation of various combinations of therapies. Vyxeos received Orphan Drug Designation by the European Commission in January 2012 and by the U.S. Food and Drug Administration (FDA) in September 2008 for the treatment of AML. Vyxeos received Promising Innovative Medicine (PIM) designation from the Medicines and Healthcare Products Regulatory Agency in the United Kingdom. Vyxeos received U.S. FDA approval and orphan drug exclusivity on August 3, 2017 for the treatment of adults with newly-diagnosed t-AML or AML-MRC.

About CombiPlex
The CombiPlex proprietary technology enables the design and rapid evaluation of various combinations of therapies to deliver enhanced anti-cancer activity. The CombiPlex technology seeks to identify the most synergistic ratio of drugs in vitro and fix this ratio in a nano-scale delivery complex that maintains the synergistic combination after administration. CombiPlex utilizes two proprietary nano-scale delivery platforms: liposomes to control the release and distribution of water-soluble drugs and drugs that are both water- and fat-soluble (amphipathic), and nanoparticles to control the release and distribution of non-water-soluble (hydrophobic) drugs.

About AML
Acute myeloid leukaemia (AML) is a blood cancer that begins in the bone marrow, which produces most of the body’s new blood cells.1 AML cells crowd out healthy cells and move aggressively into the bloodstream to spread cancer to other parts of the body.2 The median age at diagnosis is 68 years old, with rising age associated with a progressively worsening prognosis.3-4 There is also a reduced tolerance for intensive chemotherapy as patients age.5 Patients with t-AML or AML-MRC have few treatment options and some of the lowest survival rates compared to people with other forms of leukaemia.6-7 A hematopoietic stem cell transplant (HSCT) may be a curative treatment option for patients.8

On June 29, 2018 Galera Therapeutics, Inc., a clinical-stage biotechnology company focused on the development of drugs targeting oxygen metabolic pathways with the potential to transform cancer radiotherapy, reported data from the Phase 2b clinical trial evaluating GC4419, a highly selective and potent small molecule dismutase mimetic, were presented today during an oral session at the Multinational Association of Supportive Care in Cancer (MASCC) and the International Society of Oral Oncology (ISOO) 2018 Annual Meeting in Vienna, Austria (Press release, Galera Therapeutics, JUN 29, 2018, View Source [SID1234527597]).

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Trial investigator Carryn Anderson, M.D., Radiation Oncologist, University of Iowa Hospitals and Clinics, was awarded the MASCC Steven M. Grunberg Memorial Award, which recognizes the author of the highest-ranking abstract for excellent scientific achievement in supportive care in cancer. Dr. Anderson also delivered the Annual Steven M. Grunberg Memorial Lecture.

"I’m honored that my peers have recognized the clinically meaningful GC4419 data with this prestigious award," said Dr. Anderson. "GC4419 demonstrated the ability to significantly decrease the duration and incidence of severe oral mucositis, highlighting its potential to be an important new adjunct medication for head and neck cancer patients undergoing radiation therapy. There are currently no approved therapies to prevent or mitigate this common and painful side effect of cancer treatment."

"We’re delighted that Dr. Anderson has been commended with the Steven M. Grunberg Memorial Award for the GC4419 data," said Mel Sorensen, M.D., President and CEO of Galera. "Earlier this month, our Phase 2b clinical trial data were also selected to be part of the Best of ASCO (Free ASCO Whitepaper) program. These distinctions from academia speak to the significance of the data and provide further validation of GC4419’s promise to address a serious unmet need. We look forward to advancing GC4419 into the next phase of development."

About the GC4419 Phase 2b Data

The 223-patient, double blind, randomized, placebo-controlled trial evaluated the safety of GC4419 and its ability to reduce the duration of radiation-induced severe oral mucositis (SOM) in patients with locally advanced squamous cell head and neck cancer receiving seven weeks of radiation therapy plus cisplatin. Approximately 70 percent of patients receiving chemoradiotherapy develop SOM, as defined by the World Health Organization as Grade 3 or 4, which is the most debilitating side effect of the radiotherapy.

Patients in the trial were treated with either 30 mg or 90 mg of GC4419 or placebo by infusion on the days they received their radiation treatment. Patients were randomized to one of the three treatment groups (1:1:1) and the trial recruited patients in both the United States and Canada. GC4419 exhibited a safety profile comparable to placebo in the two treatment groups, and was well tolerated. In the trial’s intent-to-treat population, the 90 mg dose of GC4419 met the primary endpoint, demonstrating a statistically significant (p = 0.024) 92 percent reduction in the median duration of SOM from 19 days to 1.5 days.

In the 90 mg arm, GC4419 also demonstrated a clinically meaningful effect in pre-specified secondary endpoints (incidence and severity of SOM). GC4419 achieved a 34 percent reduction through completion of radiation (p = 0.009), and a 36 percent reduction through 60 Gy of radiation (p = 0.010), in the overall incidence of SOM, and reduced the severity of patients’ OM by 47 percent (p = 0.045).

About Oral Mucositis

Oral mucositis (OM) is a painful and problematic complication during cancer treatment, especially radiation therapy, caused by excessive superoxide generated during treatment that breaks down epithelial cells that line the mouth. Patients suffering from OM experience severe pain, inflammation, ulceration and bleeding of the mouth.

In the United States, more than 50 percent of patients with cancer receive radiotherapy at some time in their treatment. In patients with head and neck cancer, radiotherapy is a mainstay of treatment and approximately 70 percent of patients receiving chemoradiotherapy develop severe oral mucositis (SOM) as defined by the World Health Organization as Grade 3 or 4, which is the most debilitating side effect of the radiotherapy.

SOM can adversely affect cancer treatment outcomes by causing interruptions in radiotherapy, which may compromise the otherwise good prognosis for tumor control in many of these patients. SOM may also inhibit patients’ ability to eat solid food or even drink liquids, and can cause serious infections. Further, the costs of managing these side effects are substantial, particularly when hospitalization and/or surgical placement of PEG tubes to maintain nutrition and hydration are required. There is currently no drug approved to prevent or treat SOM in patients with head and neck cancer.

About GC4419

GC4419 is a highly selective and potent small molecule dismutase mimetic that closely mimics the activity of human superoxide dismutase enzymes. GC4419 works to reduce elevated levels of superoxide caused by radiation therapy by rapidly converting superoxide to hydrogen peroxide and oxygen. Left untreated, elevated superoxide can damage noncancerous tissues and lead to debilitating side effects, including oral mucositis (OM), which can limit the anti-tumor efficacy of radiation therapy. Conversion of elevated superoxide to hydrogen peroxide, which is selectively more toxic to cancer cells, can also enhance the effect of radiation on tumors, particularly with stereotactic body radiation therapy (SBRT), which produces high levels of superoxide.

GC4419 has been studied in patients with head and neck cancer, GC4419’s lead indication, for its ability to reduce the incidence and duration of radiation-induced severe oral mucositis (SOM). Results from Galera’s 223-patient, double blind, randomized, placebo-controlled Phase 2b clinical trial demonstrated GC4419’s ability to dramatically reduce the duration of SOM from 19 days to 1.5 days (92 percent), the incidence of SOM through completion of radiation by 34 percent and the severity of patients’ OM by 47 percent, while demonstrating acceptable safety when added to a standard radiotherapy regimen. In addition, in multiple preclinical studies, GC4419 demonstrated an increased tumor response to radiation therapy while preventing toxicity in normal tissue.

The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation to GC4419 for the reduction of the duration, incidence and severity of SOM induced by radiation therapy with or without systemic therapy. The FDA also granted Fast Track designation to GC4419 for the reduction of the severity and incidence of radiation and chemotherapy-induced OM.

On June 28, 2018 Corvus Pharmaceuticals, Inc. (NASDAQ:CRVS), a clinical-stage biopharmaceutical company focused on the development and commercialization of precisely targeted oncology therapies, reported publication of results of preclinical studies of CPI-444 conducted by researchers at Johns Hopkins University School of Medicine (Press release, Corvus Pharmaceuticals, JUN 28, 2018, View Source;p=RssLanding&cat=news&id=2356398 [SID1234527496]). The data showed that CPI-444 administered as monotherapy suppressed tumor growth and improved survival in animal tumor models, and CPI-444 administered in combination with anti-PD-1 therapy dramatically improved antitumor immune responses over either agent used alone. The results were published online this month in the journal Cancer Immunology, Immunotherapy (CII), in a publication titled "Inhibition of the adenosine A2a receptor modulates expression of T cell coinhibitory receptors and improves effector function for enhanced checkpoint blockade and ACT (adoptive cellular therapy) in murine cancer models," and can be accessed here.

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CPI-444, Corvus’ lead product candidate, is a selective and potent inhibitor of the adenosine A2A receptor. It is currently being evaluated in early-stage clinical trials in patients with various solid tumors as a single agent and in combination with Genentech’s atezolizumab, an anti-PD-L1 antibody.

"These newly published studies add to the growing scientific and clinical evidence of the importance of the adenosine pathway in modulating immune responses in cancer. The results provide further evidence that the A2A receptor may serve as a crucial regulator of immune response, and confirms the potential of CPI-444 in cancer therapy," said Richard A. Miller, M.D., an oncologist and co-founder, president and chief executive officer of Corvus. "CPI-444 has been studied in more than 250 patients to date both as a monotherapy and in combination with an anti-PD-L1 antibody. To our knowledge, it is the only A2A receptor antagonist to reproducibly show anti-tumor activity as a monotherapy in preclinical and clinical studies. We are currently enrolling patients in a Phase 1/1b trial in renal cell cancer and in a Phase 1b/2 trial in non-small cell lung cancer."

Results of the preclinical studies conducted by researchers at the Sidney Kimmel Comprehensive Cancer Research Center and Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins University School of Medicine, showed that CPI-444:

Administered as monotherapy suppressed tumor growth and improved survival in two animal models of colon tumors — CT26, which is very resistant to checkpoint blockade, and MC38.
Enhanced the efficacy of anti-PD-1 immunotherapy. The combination therapy dramatically improved tumor regression and animal survival in both the CT26 and MC38 colon tumor models. The effect was particularly marked in the CT26 tumor model, which showed a 70 percent cure rate.
Dramatically enhanced immune responses in models of tumor immunity, augmented immune memory responses to viral antigens, and enhanced adoptive cellular therapy (ACT) in an animal model of melanoma.
Suppressed the expression of multiple checkpoint pathways, including PD-1, LAG-3, TIM-3 and CTLA-4, on both CD8 positive and T reg cells (which play an important role in regulating antitumor immune responses). The most significant effects were seen in tumor-draining lymph nodes.
Increased the function of killer T cells (CD8+) in tumor infiltrating cells.
ABOUT CPI-444
CPI-444 is a small molecule, oral, checkpoint inhibitor designed to disable a tumor’s ability to subvert attack by the immune system by blocking the binding of adenosine in the tumor microenvironment to the A2A receptor. Adenosine, a metabolite of ATP (adenosine tri-phosphate), is produced within the tumor microenvironment where it may bind to the adenosine A2A receptor present on immune cells and block their activity. CD39 and CD73 are enzymes on the surface of tumor cells and immune cells. These enzymes work in concert to convert ATP to adenosine. In vitro and preclinical studies have shown that dual blockade of CD73 and the A2A receptor may be synergistic.

On June 28, 2018 Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN) reported that the Company will report its financial results for the second quarter ended June 30, 2018 before the US financial markets open on July 26, 2018 (Press release, Alexion, JUN 28, 2018, View Source [SID1234527498]). Following the release of the financial results, Alexion management will conduct a conference call and audio webcast at 8:00 a.m. Eastern Time (ET).

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To participate in this conference call, dial 866-762-3111 (USA) or 210-874-7712 (International), conference ID 9096048 shortly before 8:00 a.m. ET. The audio webcast can be accessed on the Investor page of View Source and an archived version will be available for a limited time following the presentation.

On June 28, 2018 Cellectar Biosciences, Inc. (Nasdaq: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted treatments for cancer, reported that the company will expand patient enrollment in the diffuse large b-cell lymphoma (DLBCL) cohort of its currently enrolling Phase 2 clinical trial of CLR 131 (Press release, Cellectar Biosciences, JUN 28, 2018, View Source [SID1234527499]).

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The response rate of the DLBCL cohort exceeded pre-specified criteria. As a result, the company will expand the cohort up to an additional 30 patients. This group represents the second of four cohorts to be expanded in this Phase 2 study. Previously the company announced the expansion of the study’s multiple myeloma (MM) cohort. Additional updates on the two remaining select B-cell lymphoma cohorts will be provided when data are available.

"Relapse or refractory DLBCL is an aggressive cancer and the initial response rates from the cohort leave us optimistic in CLR 131’s potential to have a positive impact on patients with life-threatening hematologic cancers. We continue to see clinical benefit using CLR 131 across a range of cancer types and we look forward to providing future data updates on this indication and others," stated James Caruso, president and chief executive officer of Cellectar Biosciences.

About the Phase 2 Study of CLR 131

The Phase 2 study is being conducted in approximately 10 leading cancer centers in the United States for patients with relapsed or refractory B-cell hematologic cancers. The hematologic cancers being studied include (MM, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and potentially diffuse large B-cell lymphoma (DLBCL).

The study’s primary endpoint is clinical benefit response (CBR), with additional endpoints of progression free survival (PFS), median overall survival (OS) and other markers of efficacy following a single 25.0 mCi/m2 dose of CLR 131, with the option for a second 25.0 mCi/m2 dose approximately 75-180 days later.

In addition to the CLR 131 infusion(s), MM patients will receive 40 mg oral dexamethasone weekly for up to 12 weeks. Efficacy responses will be determined by the latest International Multiple Myeloma Working Group criteria. Efficacy for all lymphoma patients will be determined according to Lugano criteria. Cellectar has been awarded approximately $2 million in a non-dilutive grant from the National Cancer Institute to help fund the trial. More information about the trial, including eligibility requirements, can be found at www.clinicaltrials.gov, reference NCT02952508.

About Diffuse Large B-Cell Lymphoma

According to the Lymphoma Research Foundation, diffuse large B-cell lymphoma (DLBCL) is an aggressive form of non-Hodgkin’s lymphoma (NHL), accounting for about 30 percent of newly diagnosed cases of NHL in the United States.

The American Cancer Society’s most recent estimates for NHL for 2018 project approximately 74,680 people (41,730 males and 32,950 females) will be diagnosed with NHL including both adults and children. They estimate that approximately 19,910 people will die from this cancer (11,510 males and 8,400 females).

DLBCL occurs in both men and women, although it is slightly more common in men. Although DLBCL can occur in childhood, its incidence generally increases with age, and roughly half of patients are over the age of 60.

DLBCL is an aggressive (fast-growing) lymphoma that can arise in lymph nodes or outside of the lymphatic system, in the gastrointestinal tract, testes, thyroid, skin, breast, bone, or brain. Often, the first sign of DLBCL is a painless, rapid swelling in the neck, underarms, or groin that is caused by enlarged lymph nodes. For some patients, the swelling may be painful. Other symptoms may include night sweats, fever, and unexplained weight loss. Patients may notice fatigue, loss of appetite, shortness of breath, or pain.

About Phospholipid Drug Conjugates (PDCs)

Cellectar’s product candidates are built upon a patented delivery and retention platform that utilizes optimized PDCs to target cancer cells. The PDC platform selectively delivers diverse oncologic payloads to cancerous cells and cancer stem cells, including hematologic cancers and solid tumors. This selective delivery allows the payloads’ therapeutic window to be modified, which may maintain or enhance drug potency while reducing the number and severity of adverse events. This platform takes advantage of a metabolic pathway utilized by all tumor cell types in all cell cycle stages. Compared with other targeted delivery platforms, the PDC platform’s mechanism of entry does not rely upon specific cell surface epitopes or antigens. In addition, PDCs can be conjugated to molecules in numerous ways, thereby increasing the types of molecules selectively delivered. Cellectar believes the PDC platform holds potential for the discovery and development of the next generation of cancer-targeting agents.

About CLR 131

CLR 131 is Cellectar’s investigational radioiodinated PDC therapy that exploits the tumor-targeting properties of the company’s proprietary phospholipid ether (PLE) and PLE analogs to selectively deliver radiation to malignant tumor cells, thus minimizing radiation exposure to normal tissues. CLR 131, is in a Phase 2 clinical study in relapsed or refractory (R/R) MM and a range of B-cell malignancies and a Phase 1 clinical study in patients with (R/R) MM exploring fractionated dosing. In 2018 the company plans to initiate a Phase 1 study with CLR 131 in pediatric solid tumors and lymphoma, and a second Phase 1 study in combination with external beam radiation for head and neck cancer.