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 29, 2018 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS) reported that the U.S. Food and Drug Administration (FDA) has notified the company that it has lifted the clinical hold on APTO-253, Aptose’s investigational drug for hematologic cancers (Press release, Aptose Biosciences, JUN 29, 2018, View Source;p=RssLanding&cat=news&id=2356603 [SID1234527515]). APTO-253 is the only known clinical-stage molecule that has the potential to directly inhibit expression of the MYC oncogene, shown to be a causative factor in many malignancies, including acute myeloid leukemia (AML).

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Up to fifteen clinical centers are expected to participate in the Phase 1b trial, and the screening and dosing will resume as soon as practicable for patients with relapsed or refractory AML or with high risk myelodysplastic syndromes (MDS). Recent data also highlight the role of MYC gene dysregulation in B-cell malignancies1, and Aptose hopes to pursue this patient population in the coming months.

The Phase 1b trial of APTO-253 had been placed on clinical hold as a consequence of an event that occurred at a clinical site with the infusion procedure. Ultimately, a root cause investigation determined that the event resulted from chemistry and manufacturing based issues, all of which were incorporated into a Chemistry, Manufacturing and Control (CMC) amendment to the Investigational New Drug (IND) application.

"We are eager to return APTO-253 back into the clinic," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "Our understanding of this molecule has evolved dramatically, and we are excited to deliver a MYC gene expression inhibitor to patients with debilitating hematologic malignancies."

About the Study

The Phase 1b, multicenter, open-label, dose-escalation clinical trial of APTO-253 is designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamic responses and efficacy of APTO-253 as a single agent and determine the recommended Phase 2 dose. APTO-253 will be administered once weekly, over a 28-day cycle. The dose escalation cohort of the study could potentially enroll up to 20 patients with relapsed or refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS). The study is designed to then transition, as appropriate, to single-agent expansion cohorts in AML and MDS.

MYC dysregulation is a common driver in many malignancies, making it an attractive therapeutic target. Repression of MYC expression by bromodomain (BET) inhibitors has proven effective at triggering apoptosis in leukemia cells; however, inhibition of bromodomain proteins can cause severe toxicities and myelosuppression due to the presence of bromodomain proteins on all active genes. Unlike BET inhibitors and other cancer chemotherapies, APTO-253 acts through a distinct targeted mechanism. As a first in class, small molecule MYC inhibitor, APTO-253 may be particularly appropriate for the management of patients having AML and other hematologic malignancies with compromised bone marrow function. Earlier this month, Aptose announced the publication of preclinical data further elucidating the mechanism of action of APTO-253 (here).

About APTO-253

APTO-253 is a clinical-stage small molecule targeted therapeutic agent that inhibits expression of the MYC oncogene, leading to cell cycle arrest and programmed cell death (apoptosis) in human-derived solid tumor and hematologic cancer cells. The MYC oncogene is overexpressed in hematologic cancers, including acute myeloid leukemia (AML). Aptose researchers have reported the ability of APTO-253 to induce cell death, or apoptosis, in multiple blood cancer cell lines including AML, as well as in vitro synergy with various classes of conventional approved and investigational therapies for AML or myelodysplastic syndromes (MDS). New findings reveal that APTO-253 might also serve certain solid tumor patients with BRCA1/2 mutations, but without causing toxicity to the normal bone marrow functions.

On June 29, 2018 Biologics, Inc., a McKesson Specialty Health oncology, neurology and complex care pharmacy services company, has been selected by Array BioPharma, Inc. to be in the limited distribution network for the combination therapy BRAFTOVITM (encorafenib) and MEKTOVI (binimetinib) for the treatment of patients with unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by a U.S. Food and Drug Administration (FDA) approved test (Press release, Biologics, JUN 29, 2018, View Source [SID1234527519]).

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"Advanced BRAF-mutant melanoma is a serious and deadly type of skin cancer. Nearly half of melanoma patients who are diagnosed with the cancer after it has already spread have the BRAF mutation," said Brandon Tom, VP, Commercial Services, McKesson Specialty Health. "BRAFTOVI and MEKTOVI represent an important new targeted treatment, and we are looking forward to helping to bring this new option to the metastatic melanoma community."

BRAFTOVI and MEKTOVI were approved by the FDA on June 27, 2018 based on clinical data from the Phase 3 COLUMBUS trial, published in the Lancet Oncology.1 More information about these products can be found at www.braftovimektovi.com.

Metastatic melanoma is the most life-threatening type of skin cancer and is associated with low survival rates. 2,3 Approximately half of the estimated 200,000 new cases of melanoma diagnosed worldwide each year have BRAF mutations, a key target in the treatment of metastatic melanoma. 2,4,5

Biologics’ oncology specialty pharmacy is committed to providing patient-centric care throughout the patient’s cancer journey. The company is recognized across the industry for its high level of customer service and its innovative high-touch patient care model that supports patients with a multidisciplinary care team. Each team includes a pharmacist with in-depth knowledge of oncology pharmaceuticals, an experienced oncology nurse and a financial counselor who is familiar with various financial assistance programs and organizations that help cancer patients. This highly skilled care team works together to develop individualized care plans that address each patient’s unique clinical, financial and emotional needs and that streamline communication back to the treating provider, empowering high-quality care and optimal outcomes.

Physicians may submit prescriptions to Biologics via phone (800-850-4306), fax (800-823-4506) or eScribe. For electronic prescribing systems, physicians may search for Biologics within their EMR system.

On June 28, 2018 MolMed S.p.A. (MLMD.MI), a medical biotechnology company focusing on research, development, manufacturing, and clinical validation of cell & gene therapies to treat cancer and rare diseases and AbCheck s.r.o., a technology company focusing on the discovery and optimization of high-quality human antibodies, reported that they have entered into a three-year Master Agreement aimed at providing MolMed with selected and optimized antibodies for the development of new Chimeric Antigen Receptors (CARs), targeting both liquid and solid tumors (Press release, MolMed, JUN 28, 2018, View Source [SID1234527504]).

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Under the agreement, AbCheck will use its proprietary discovery platform to select, optimize and deliver multiple human single-chain variable fragments (scFvs), specifically recognizing each MolMed target candidate. ScFvs are the extracellular regions of the CAR responsible for antigen recognition and binding, conferring specificity to the CAR.

The new and optimized scFvs delivered by AbCheck will allow MolMed to expand its proprietary pipeline in both autologous CAR-T and future allogenic CAR-NK platforms.

Riccardo Palmisano, MolMed CEO, commented: "This new collaboration plays a key role to complete the picture of the planned and announced enlargement of our CAR pipeline. Leveraging on the unique experience that we developed on CAR T CD44v6, now close to clinical stage in acute myeloid leukemia and multiple myeloma and on the recently signed partnership with Glycostem, with this agreement with AbCheck, a company with extensive expertise in antibodies selection and boasting partnerships with relevant companies and institutions in the CAR field, MolMed is fully prepared to build a robust autologous and allogeneic original CAR T pipeline, able to target both liquid and solid tumors".

Volker Lang, Managing Director of AbCheck, added: "AbCheck is recognized for its proven capability to reliably deliver high-quality human antibodies suitable for clinical development. We are very pleased to employ our unique technology suite to support MolMed’s dedicated team in adding novel therapeutic options to its diverse pipeline. Both CAR-Ts and CAR-NKs represent promising novel immuno-oncology approaches and we are confident that AbCheck’s abilities in antibody discovery and optimization will be an important asset in developing such approaches."

On June 28, 2018 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN:ATNM) ("Actinium" or "the Company"), reported that Dr. Joseph Jurcic, Director of the Hematologic Malignancies Section and Professor of Medicine at Columbia University Medical Center, has initiated Actimab-A MRD, a new clinical trial for patients with AML who are in remission but have detectable minimal residual disease (MRD) (Press release, Actinium Pharmaceuticals, JUN 28, 2018, View Source [SID1234527514]). The trial will study the safety/tolerability of Actimab-A in the postremission consolidation setting and include dose finding analyses. The trial will also study the impact of Actimab-A on minimal residual disease (MRD) as well as progression-free (PFS) and overall survival (OS) rates. The investigational new drug (IND) application for this trial has been cleared by the FDA.

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Together with Dr. Jurcic, Actinium will host a webcast to discuss the planned trial, participation information is as follows:

Date: July 10, 2018
Time: 8:00 AM ET
Registration Link: View Source
Telephone participation: U.S./Canada Toll Free: (855) 427-0225 or (718) 865-8336
Conference ID: 2540

Dr. Joseph Jurcic said, "Although patients with AML can achieve complete remissions with induction therapy, the rate of relapse remains high resulting in high mortality rates. Strong evidence exists that minimal residual disease is a major driver of disease relapse and clearly demonstrates the need for improved consolidation therapies that can effectively target MRD. Based on the clinical profile of Actimab-A to date, I am excited to study this therapy for use as a consolidation therapy. It will be a significant advancement for AML patients if this trial shows the ability to target MRD and reduce relapse rates."

There are an estimated 21,000 patients diagnosed with AML annually in the United States and over 350,000 cases of AML worldwide. According to the National Cancer Institute, 5-year survival for AML patients under age 65 is 45% while 5-year survival for patients over 65 is 6% with the median age of diagnosis of AML patients being 68. With curative intent induction chemotherapy, 45% – 65% of patients can achieve complete remission but up to 80% of patients will relapse despite postremission consolidation treatment. Currently, non-transplant-based consolidation therapies consist mainly of chemotherapy such as high-dose Cytarabine. The presence of MRD has been shown to be associated with higher rates of relapse and earlier relapse in multiple studies. Recently, the FDA approved a therapy for patients with a certain type of B-cell leukemia who are in remission but have detectable MRD.

Dr. Mark Berger, Actinium’s Chief Medical Officer said, "Actimab-A has many points of differentiation that I feel make it well suited to address MRD treatment as consolidation therapy. Given that patients receive chemotherapy as induction therapy, I believe it is important to develop a non-chemotherapy based consolidation therapy that has fewer toxicities and side effects than chemotherapy. This is particularly important for older patients, who do not have the same ability to tolerate high dose therapies as young patients, and who are the majority of patients with AML. We believe our ARC or Antibody Radiation Conjugate approach enables precision targeting of residual AML cells and potentially provide a means by which MRD can be eliminated and relapse rates lowered. We look forward to working with Dr. Jurcic to execute this important trial for AML patients."

Sandesh Seth, Actinium’s Chairman and CEO said, "We are excited by the continued expansion of our CD33 program and intend to solidify our position as the best-in-class CD33 targeting therapy by demonstrating its potential in multiple diseases and multiple indications. Expansion into the consolidation setting is an important achievement towards this end. Further, the application of our therapy for MRD, strategically aligns us with the forefront of scientific exploration in a clinical setting. We believe the breadth of our CD33 program is unmatched given that we are now studying our ARC not only in multiple AML settings including induction, consolidation and in relapsed/refractory disease but also in multiple myeloma as a therapeutic, and in MDS as targeted conditioning to enable a bone marrow transplant. With this important trial poised to start and clinical data expected from our ongoing trials, we are confident in our ability to realize the intrinsic value of this program and advance these trials to benefit the greatest number of patients."

About Actimab-A
Actimab-A is an antibody radio-conjugate (ARC) comprised of the anti-CD33 monoclonal antibody lintuzumab labeled with the radioisotope actinium-225. CD33 is a marker expressed on AML cells of virtually all affected patients. Actimab-A has been studied in over 100 patients to date and is the only CD33 targeting agent being studied in a broad range of diseases in which the CD33 antigen is expressed, including AML, myelodysplastic syndrome (MDS) and multiple myeloma.

Actinium-225 is highly differentiated radioisotope that emits high amounts of energy through the release of four alpha-particles that can cause double-stranded breaks in DNA with known resistance mechanisms to Actinium-225. Given the limited distance of its energy in the body, it is potentially sparing of non-targeted cells leading to better tolerability and less toxicities.

Actimab-A has been granted Orphan Drug Designation from both the U.S. Food and Drug Administration and the European Medicines Agency for newly diagnosed AML in patients age 60 and above.