On December 27, 2017 Actinium Pharmaceuticals, Inc. (NYSE American:ATNM) ("Actinium" or "the Company") reported that the Independent Data Monitoring Committee (DMC) for the Pivotal Phase 3 SIERRA Trial (Study of Iomab-B for Elderly Relapsed or Refractory AML) of Iomab-B (131I apamistamab) completed its review of the data available from the trial at time of analysis (Press release, Actinium Pharmaceuticals, DEC 27, 2017, View Source [SID1234522781]). The DMC recommended that the trial continue to enroll patients as planned. The SIERRA Trial is a 150 patient, controlled, multi-center pivotal study that is comparing Iomab-B followed by a bone marrow transplant (BMT) to physician’s choice of salvage chemotherapy in patients with relapsed or refractory acute myeloid leukemia (AML) that are age 55 and above. The primary endpoint of the trial is durable Complete Remission (dCR) at 6 months.

Dr. Mark Berger, Actinium’s Chief Medical Officer said, "The DMC’s review and recommendations for Iomab-B are in line with our expectations at this stage of the trial and are important given the high unmet need of these patients with current therapies. A bone marrow transplant is the only potential cure for these patients and safer myeloablation could have a major impact on patient outcomes. We believe that Iomab-B will provide safer myeloablation for AML patients seeking a bone marrow transplant, which will expand patient access to transplant, improve rates of transplant engraftment, and improve survival outcomes. We are encouraged that the DMC reviewed initial safety data from the first 20 patients enrolled in the trial at its regularly scheduled late November meeting. We remain confident that we will be able to complete patient enrollment by the end of 2018 due to the significant progress we have made this year setting up the foundations for the trial and also due to certain other factors which are detailed below."

Enrollment activity for the SIERRA trial has continued to build as a function of site activation, familiarity of the site with the patient protocols for using Iomab-B and investigator experience with the drug candidate versus the control. Actinium announced that the fifteenth SIERRA clinical trial site had been activated at the end of October 2017. The SIERRA clinical trial sites are some of the leading and highest volume BMT centers in the US including the MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center, the Mayo Clinical, the Fred Hutchinson Cancer Research Center and many others. Together, these active sites account for approximately one third of bone marrow transplant related volume. Actinium previously commented that once a site has treated its initial patient with Iomab-B, recruitment and enrollment accelerates at that site. In addition, to continuing to devote attention to activated sites in order to meet enrollment objectives, Actinium intends to continue to also focus on activating additional clinical trial sites and educating site staff in order to build on the strong foundation for patient enrollment. In 2018, Actinium expects to open the SIERRA trial at 5-7 additional clinical trial sites including sites in Canada where the company received clearance to initiate the trial from Health Canada in 2017.

In addition, Actinium announced that it will amend the protocol of the SIERRA trial to expand the salvage chemotherapy regimens available in the control arm of the study, following the feedback from investigators at trial sites and the advice of its Scientific Advisory Board that was convened during the recent ASH (Free ASH Whitepaper) meeting. The Company expects that being responsive to investigator suggestions and amending the protocol removes a hindrance to enrollment at some of the major sites as it provides investigators with the ability to better enroll patients. In addition to the SAB meeting, Iomab-B was featured at a PeerView CME-Certified event on Friday, December 8, 2017 titled "A Master Class on Building Better Therapy for AML: Making the Most of an Increasing Number of Innovative Options" where it was highlighted by Dr. Amir Fathi of Mass General Hospital Cancer Center to several hundred physician attendees. The Company expects to follow-up on the interest generated from this event in order to support the objectives of the SIERRA trial and also to prepare Iomab-B for commercialization.

Actinium also reported that it has successfully supplied dosimetric and therapeutic doses as needed to all patients in the study arm and to all of the patients that have crossed over to the Iomab-B arm from the control arm thus far. Patients that cross over from the control arm are counted as failures for the primary endpoint of durable Complete Remission of at least 6 months. The Company has stated that in 2017 it manufactured additional antibody at commercial scale, and has sufficient quantities to account for the current trial and the planned potential label expansion initiatives in 2018.

Sandesh Seth, Actinium’s Chairman and CEO said, "Iomab-B is a drug candidate that is not only first in class with no visible competition in clinical development but it also has the potential to establish a new treatment paradigm for bone marrow conditioning. The SIERRA trial is the first multi-center, company sponsored trial for Iomab-B and it is supported by data generated at the Fred Hutchinson Cancer Research Center in several hundred patients in multiple hematologic indications, including the patient population of the SIERRA trial. Actinium has achieved significant progress this year not only by opening the trial at some of the highest volume transplant centers but conducting educational efforts to raise the profile of this important therapeutic and potentially life saving therapeutic option. The progress made in enrollment and the validation of our assumptions regarding the trial safety and efficacy makes this initial DMC report incredibly exciting for us. We look forward to continuing to progress Iomab-B concurrent with our ever-growing focus, as exemplified by the latest initiative of Actimab-MDS, on developing treatments for superior myeloablation in multiple indications, which we believe to be a significant value creation opportunity. We are incredibly proud that our supply chain team has successfully delivered doses to all patients in the SIERRA trial including crossover patients while simultaneously supplying drug to all patients in the Actimab-A trial and Actimab-M trials and that our clinical team has opened up nearly 30 trial sites across our clinical trials. We note also that the strengthened clinical development team has enrolled more patients since June of 2017 than had been enrolled in the past five years. This combination of the ability to successfully enroll patients and establish a reliable supply chain into a network of leading hospitals that represent over a third of bone marrow transplant procedure volume is proving to be an invaluable clinical asset that we hope to leverage into a value enhancing asset as we look ahead to our next phase of growth."

The SIERRA trial is expected to complete patient enrollment by the end of 2018 which is in line with prior guidance from the Company. The trial will have safety analyses by an independent Data Monitoring Committee when 25%, 50% and 75% patient enrollment has been reached. Also, two ad-hoc efficacy analyses may be requested by Actinium after 70 and/or 110 patients have engrafted and given enough time to achieve the primary endpoint of durable complete remission at six months post treatment.

About Iomab-B

Iomab-B (131I apamistamab) is Actinium’s lead product candidate that is currently being studied in a 150-patient, multicenter pivotal Phase 3 clinical trial in patients with relapsed or refractory acute myeloid leukemia who are age 55 and above. Upon approval, Iomab-B is intended to prepare and condition patients for a bone marrow transplant, also referred to as a hematopoietic stem cell transplant, which is often considered the only potential cure for patients with certain blood-borne cancers and blood disorders. Iomab-B targets cells that express CD45, a pan-leukocytic antigen widely expressed on white blood cells with the monoclonal antibody, BC8, labeled with the radioisotope, iodine-131. By carrying iodine-131 directly to the bone marrow in a targeted manner, Actinium believes Iomab-B will avoid the side effects of radiation on most healthy tissues while effectively killing the patient’s cancer and marrow cells. In a Phase 2 clinical study in 68 patients with advanced AML or high-risk myelodysplastic syndrome (MDS) age 50 and older, Iomab-B produced complete remissions in 100% of patients and patients experienced transplant engraftment at day 28. Iomab-B was developed at the Fred Hutchinson Cancer Research Center where it has been studied in almost 300 patients in a number of blood cancer indications, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), Hodgkin’s disease (HD), Non-Hodgkin lymphomas (NHL) and multiple myeloma (MM). Iomab-B has been granted Orphan Drug Designation for relapsed or refractory AML in patients 55 and above by the U.S. Food and Drug Administration and the European Medicines Agency.

On December 27, 2017 Oncolytics Biotech Inc. (TSX: ONC) (OTCQX: ONCYF) (Oncolytics or the Company), a biotech company developing REOLYSIN, also known as pelareorep, an intravenously delivered immuno-oncolytic virus that activates the innate and adaptive immune systems to turn ‘cold’ tumors ‘hot’, reported that data from REO 024 will be presented at the 2018 Gastrointestinal Cancers Symposium sponsored by ASCO (Free ASCO Whitepaper), January 18 – 20, 2018, in San Francisco (Press release, Oncolytics Biotech, DEC 27, 2017, View Source [SID1234522782]). The poster presentation by Dr. Devalingam Mahalingam, M.D. Ph.D., Associate Professor of Medicine (Hematology and Oncology) at the Feinberg School of Medicine, Northwestern University, will present clinical data evaluating intravenous administration of pelareorep in combination with pembrolizumab (KEYTRUDA) and chemotherapy in patients with advanced or metastatic pancreatic adenocarcinoma.

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"I’m thrilled that Dr. Mahalingam will have the opportunity to present data from the REO 024 study combining pelareorep with Merck’s Keytruda and chemotherapy," said Dr. Matt Coffey, President and CEO of Oncolytics Biotech. "While our focus remains on metastatic breast cancer, we continue to be very interested in the potential to treat pancreatic cancer patients. Our NCI-8601 study demonstrated an increase in landmark survival at two years in pancreatic patients from nine percent to twenty percent, when comparing pelareorep plus carboplatin to carboplatin alone. Our REO 017 study improved overall two-year survival in pancreatic patients from historical measures of four to five percent to twenty-four percent, when comparing pelareorep plus gemcitabine to gemcitabine alone. We believe there is an obvious therapeutic effect in pancreatic cancer and look forward to this presentation in January."

Abstract number: 283
Title: A study of pelareorep in combination with pembrolizumab and chemotherapy in patients (pts) with relapsed metastatic adenocarcinoma of the pancreas (MAP)

Poster Session: Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Date/Time: January 19, 11:30 AM-1:00 PM; 5:30 PM-6:30

About REOLYSIN/Pelareorep
REOLYSIN, also known as pelareorep, is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers.

On December 26, 2017 DelMar Pharmaceuticals, Inc. (NASDAQ: DMPI) ("DelMar" or the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for the company’s lead product candidate, VAL-083, in recurrent glioblastoma (rGBM) (Press release, DelMar Pharmaceuticals, DEC 26, 2017, View Source [SID1234522768]).

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"The Fast Track designation marks an important milestone in the development of VAL-083 as a potential new therapy for cancer patients with limited or no treatment options," said Saiid Zarrabian, interim chief executive officer at DelMar. "We appreciate the FDA’s recognition that the VAL-083 program addresses a significant unmet need in rGBM as we continue to evaluate this agent in patients with multiple tumor types."

This Fast Track status applies to two ongoing clinical trials sponsored by DelMar Pharmaceuticals to evaluate VAL-083 as a potential treatment for rGBM. These trials include:

A Phase 2 study in bevacizumab-naïve MGMT-unmethylated GBM patients conducted in collaboration with The University of Texas MD Anderson Cancer Center; and
A Phase 3 study of patients whose disease has progressed following prior treatment with temozolomide and bevacizumab (the STAR-3 trial).
Fast track designation is designed to expedite the review of drugs that show promise in treating life-threatening diseases and address unmet medical needs, with the goal of getting new treatments to patients earlier. Fast Track designation provides sponsors with an opportunity for increased frequency of communication with FDA to ensure an optimal development plan and to collect appropriate data needed to support drug approval.

Additional benefits of the Fast Track designation may include an Accelerated Approval, a Priority Review, and a Rolling Review. Accelerated Approval is granted to drugs that demonstrate an effect on a surrogate, or intermediate endpoint reasonably likely to predict clinical benefit. Priority Review shortens the FDA review process for a new drug from ten months to six months, and is appropriate for drugs that demonstrate significant improvements in both safety and effectiveness of an existing therapy. Rolling Review provides a drug company the opportunity to submit completed sections of its New Drug Application (NDA) for review by the FDA. Typically, NDA reviews do not commence until the drug company has submitted the entire application to the FDA. Through the Fast Track designation, the FDA attempts to ensure that questions raised during the drug development process are resolved quickly, often leading to earlier approval and increased access for patients.

Outside of rGBM, DelMar has initiated a Phase 2 clinical trial of VAL-083 in newly-diagnosed MGMT-unmethylated GBM. DelMar also recently received notice of allowance from the FDA of an IND for a Phase 1/2 trial of VAL-083 in patients with recurrent platinum-resistant ovarian cancer.

"Our ongoing VAL-083 clinical development program is supported by extensive preclinical research into the agent’s unique mechanism of action, as well as promising data from prior clinical trials sponsored by DelMar and the National Cancer Institute," added Mr. Zarrabian. "We are enthusiastic about the potential of VAL-083 to offer a meaningful clinical benefit to patients with rGBM and for the opportunity to expedite the regulatory process through the FDA’s Fast Track program."

About VAL-083

VAL-083 (dianhydrogalactitol) is a "first-in-class," DNA-targeting agent that introduces interstrand DNA cross-links at the N7-position of guanine leading to DNA double-strand breaks and cancer cell death. VAL-083 has demonstrated clinical activity against a range of cancers including GBM and ovarian cancer in historical clinical trials sponsored by the U.S. National Cancer Institute (NCI). DelMar has demonstrated that VAL-083’s anti-tumor activity is unaffected by common mechanisms of chemoresistance in vitro. Further details regarding these studies can be found at View Source

VAL-083 has been granted an orphan drug designation 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.

On December 26, 2017 Dr. Reddy’s Laboratories Ltd (BSE: 500124, NSE: DRREDDY, NYSE: RDY) reported that it has launched Melphalan Hydrochloride for Injection, a therapeutic equivalent generic version of Alkeran (melphalan hydrochloride) for Injection in the United States market approved by the U.S. Food and Drug Administration (USFDA) (Press release, Dr Reddy’s, DEC 26, 2017, View Source [SID1234522769]).

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The Alkeran brand and generic had U.S. sales of approximately $107 million MAT for the most recent twelve months ending in October 2017 according to IMS Health*.

Dr. Reddy’s Melphalan Hydrochloride for Injection is available in a carton containing one singledose clear glass vial of freeze-dried melphalan hydrochloride equivalent to 50 mg melphalan and one 10 mL clear glass vial of sterile diluent.

On December 26, 2017 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS) reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to CG’806, a highly potent pan-FLT3/pan-BTK inhibitor, for the treatment of patients with acute myeloid leukemia (AML) (Press release, Aptose Biosciences, DEC 26, 2017, View Source;p=RssLanding&cat=news&id=2324031 [SID1234522772]). AML is a particularly devastating cancer of the blood and bone marrow and is the most common type of acute leukemia among adults, with an annual incidence of approximately 21,000 patients and causing more than 10,000 deaths each year in the U.S.

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"We are pleased that the FDA has recognized the unique potential of CG’806 to address AML and has assigned CG’806 the status of orphan drug designation," said William G. Rice, Ph.D., Chairman, President and CEO. "Results from non-clinical studies that we and our research collaborators have generated are promising and give reason for our eagerness to begin clinical trials in both AML and B-Cell malignancies in 2018."

AML cells utilize multiple forms of the FLT3 receptor tyrosine kinase and other pathways to promote rapid proliferation and to escape the inhibitory activities of many therapeutics. CG’806 is a highly potent inhibitor that simultaneously targets all known forms of FLT3 and other key oncogenic pathways that drive the proliferation of AML cancer cells, thereby providing CG’806 with a broad range of activity against AML and a strategy to delay mutational escape.

The FDA’s Office of Orphan Drug Products assigns orphan drug designation to support the development of medicines for underserved patient populations, or rare disorders, that affect fewer than 200,000 people in the United States. Orphan drug designation provides Aptose certain benefits, including market exclusivity upon regulatory approval if received, exemption of FDA application fees and tax credits for qualified clinical trials.

About CG’806

CG‘806 is an oral, first-in-class pan-FLT3/pan-BTK inhibitor. This small molecule demonstrates potent inhibition of all wild type and mutant forms of FLT3 tested (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), suppresses multiple oncogenic pathways operative in AML, eliminates AML tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with FLT3-driven AML. Likewise, CG’806 demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser mutant forms of the BTK enzyme, as well as other oncogenic kinases operative in B cell malignancies, suggesting CG’806 may also be developed for CLL and MCL patients that are resistant/refractory/intolerant to covalent BTK inhibitors.