On January 4, 2018 Rasna Therapeutics, Inc. (OTCQX: RASP), a clinical stage biotechnology company focused on the development of disease-modifying drugs for hematological malignancies, reported follow up Phase II clinical data showing that 4 out of 9 (44%) evaluable AML patients carrying the NPM1 gene mutation treated with actinomycin D ("Act D"), achieved complete remission (CR) (Press release, Rasna Therapeutics, JAN 4, 2018, View Source [SID1234522893]). Treatment with Act D was well-tolerated except that patients experienced oral mucositis as the major toxicity. Rasna Therapeutics has developed a proprietary nanoparticle based formulation of Act D (RASP-101), which is anticipated to maximize efficacy while minimizing oral mucositis. RASP-101 could potentially be a first-in-class modality for treatment of NPM1-mutated acute myeloid leukemia (AML).
NPM1-mutated AML is a specific genetic leukemia entity that accounts for approximately one-third cases of AML in adults. As we reported previously, intravenous treatment of refractory or relapsed NPM1-mutated AML patients with Act D (12.5 µg or 15 µg/day) for 5 consecutive days produced hematological complete response in some of them (Falini et al., N Eng J Med. 373: 12, 2015).

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In a follow-up phase II clinical study (ActD-AML-PG01, EudraCT 2014-000693-18) in refractory/relapse (R/R) AML patients carrying NPM1 gene mutation, treatment with Act D at 15 µg/kg/day for 5 days every 28 days induced CR in 4 out of the 9 evaluable patients (44.4%) with only 1 or 2 cycles of therapy. Three out of the 4 (75%) patients who obtained CR relapsed after 3, 5 and 7 months, respectively. One patient underwent haploidentical allogeneic PBSC transplantation at 3 months after CR achievement and is alive in molecular CR (MRD-negative) after 24 months.

"The precise mechanism of action of Act D in NPM1-mutated AML is still not clearly understood. Follow up data confirms our earlier findings and further support the use of Act D to induce complete hematological remissions with possible long-term molecular responses in NPM1-mutated AML patients. To note, our first previously reported NPM1-mutated AML patient (resistant to hypomethylating therapy) treated with Act D remains in molecular remission at over 3 years since CR achievement," said Dr. Brunangelo Falini, a member of the scientific advisory board of Rasna Therapeutics, Inc.

"We have developed a proprietary formulated Act D (RASP-101), which we anticipate will produce a superior clinical outcome with improved efficacy and safety profile. Emerging data from the multicenter clinical studies will allow us to develop a biomarker strategy to select responsive patients and improve clinical outcome for this unmet clinical need" commented Alessandro Padova, Chairman of Rasna.

About Actinomycin D (Dactinomycin)
Actinomycin D, also known as dactinomycin, a cytotoxic antibiotic produced by Streptomyces parvullus, was approved for medical use in the United States in 1964. It is on the World Health Organization’s List of Essential Medicines, the most effective and safe medicines needed in a health system. It is believed to work by blocking RNA synthesis. The drug has been used to treat a number of types of cancers, including Wilms tumor, rhabdomyosarcoma, Ewing’s sarcoma, trophoblastic neoplasm, testicular cancer, and certain types of ovarian cancer.

About Dr. Brunangelo Falini, M.D.
Brunangelo Falini is the head of the Institute of Hematology and Hemopoietic Stem Cell Transplantation at the University of Perugia, Perugia, Italy. His research activity has mainly focused on the genetic characterization of lymphomas and leukemias using monoclonal antibodies and, more recently, NGS technologies. He led the research group who discovered NPM1 mutations in AML in 2005 and the BRAF-V600E mutation in hairy cell leukemia in 2011. Both these seminal discoveries have already translated into a better diagnosis and therapy of patients affected by these hematological malignancies. Dr. Falini is the recipient of numerous prestigious prizes, including the "Josè Carreras Award" from EHA (Free EHA Whitepaper) (Barcelona, 2010), the "Leopold Griffuel Prize" from ARC (Paris, 2015) and the "Prize for Excellence in Medicine" from the American-Italian Cancer Foundation (New York, 2017).

On January 4, 2018 Cellectar Biosciences, Inc. (Nasdaq: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported that company management will be participating in Biotech Showcase 2018 taking place January 8-10, 2018 at the Hilton San Francisco Union Square (Press release, Cellectar Biosciences, JAN 4, 2018, View Source [SID1234522906]). James Caruso, president and chief executive officer of Cellectar Biosciences, will present a company overview and update on January 10, 2018 at 10:00 a.m. Pacific time.

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Mr. Caruso’s presentation will be webcast live at View Source;tp_key=5c62464b98 and on the Events section of the company’s website where it will also be archived.

About Phospholipid Drug Conjugates (PDCs)

Cellectar’s product candidates are built upon its patented cancer cell-targeting delivery and retention platform of optimized phospholipid ether-drug conjugates (PDCs). The company deliberately designed its phospholipid ether (PLE) carrier platform to be coupled with a variety of payloads to facilitate both therapeutic and diagnostic applications. The basis for selective tumor targeting of our PDC compounds lies in the differences between the plasma membranes of cancer cells compared to those of normal cells. Cancer cell membranes are highly enriched in lipid rafts, which are glycolipoprotein microdomains of the plasma membrane of cells that contain high concentrations of cholesterol and sphingolipids, and serve to organize cell surface and intracellular signaling molecules. PDCs have been tested in more than 80 different xenograft models of cancer.

On January 4, 2018 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3 stage biopharmaceutical company focused on discovering and developing novel small molecule drug candidates to treat cancer, with a primary focus on Myelodysplastic Syndromes (MDS), reported that it has entered into a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI), part of the National Institutes of Health (NIH) (Press release, Onconova, JAN 4, 2018, View Source [SID1234522892]). Under the terms of the CRADA, the NCI will conduct research, including preclinical laboratory studies and a clinical trial, on rigosertib in pediatric cancer associated RASopathies.

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The RASopathies are a group of rare diseases which share a well-defined molecular basis in expression or defects involving Ras Effector Pathways. They are usually caused by germline mutations in genes that alter the RAS subfamily and mitogen-activated protein kinases that control signal transduction, and are among the most common genetic syndromes. Together, this group of diseases can impact more than 1 in 1000 individuals, according to RASopathiesNet.

Dr. Steve Fruchtman, Chief Medical Officer of Onconova, noted: "We are excited about the potential of our collaboration with the Pediatric Oncology Branch at NCI’s Center for Cancer Research in the study of rigosertib in children with both hematological and solid tumors that are driven by the Ras pathway. This collaboration could lead to important advances in the treatment of these refractory tumors. This novel approach directed at a specific mechanism driving the underlying neoplasm is the basis of personalized medicine for these indications".

As part of the CRADA, Onconova will provide rigosertib supplies and initial funding towards non-clinical studies. The NCI will fund the majority of the research, including the cost of the clinical trial, which is expected to start in 2018. A clinical trial protocol has been developed and will be reviewed by the Institutional Review Board.

Onconova is also collaborating with academic researchers and patient advocacy groups interested in developing novel therapeutics to address the needs of these patients. In October 2017, Onconova held a Key Opinion Leader Breakfast Symposium in New York City to bring attention to this unmet medical need and the potential for rigosertib in RASopathies. The meeting featured presentations by Bruce D. Gelb, M.D. (Mount Sinai, New York) and Elliot Stieglitz, M.D. (University of California, San Francisco), alongside Dr. Fruchtman. In July 2017, Onconova also presented a summary of its targeted approach at a symposium organized by RASopathiesNet.org.

While the NCI will conduct a trial for RASopathy related cancers in pediatric patients, Onconova will focus on Juvenile Myelomonocytic Leukemia (JMML), a well-described RASopathy affecting children which is incurable without an allogenic hematopoietic stem cell transplant.

Additional information highlighting Onconova’s approach to studying rigosertib in RAS mediated diseases can be found in the presentation, "Strategies to RASopathies and JMML," located in the "Scientific Presentations" section of Onconova’s website.

For Patients

Patients interested in enrolling please contact NCI’s toll-free number 1-800-4-Cancer (1-800-422-6237) (TTY: 1-800-332-8615).

On January 4, 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 its Phase 2b clinical trial of lead product candidate GC4419 for the treatment of severe oral mucositis (SOM) in patients with head and neck cancer will be presented during an oral presentation at the 2018 Multidisciplinary Head and Neck Cancers Symposium being held February 15-17, 2018, at The Westin Kierland Resort & Spa in Scottsdale, Ariz (Press release, Galera Therapeutics, JAN 4, 2018, View Source [SID1234522908]).

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Details of the presentation are as follows:

Abstract ID: 20496
Title: GC4419, a small molecule superoxide dismutase (SOD) mimetic: Randomized, placebo (PBO)-controlled, double blind trial to reduce oral mucositis (OM) from chemoradiotherapy (CRT) in patients (pts) with oral cavity (OC) or oropharyngeal (OP) carcinoma (OCC)
Presentation #: LBA2
Session: Breakout Session II: Survivorship and Acute and Late Effects
Date/Time: Friday, February 16, 2018, 3-4:30 p.m. MT
Presenter: Carryn M. Anderson, M.D., Department of Radiation Oncology, University of Iowa

"We are very pleased with the robust results of this clinical trial, one of the largest ever conducted for this indication, and look forward to presenting the data at this important meeting for patients with head and neck cancer," said Mel Sorensen, M.D., President and CEO of Galera. "We believe GC4419, which leverages our dismutase mimetic platform, has the potential to represent an important new treatment approach for patients with chemoradiotherapy-related severe oral mucositis."

Co-sponsored by the American Society for Radiation Oncology (ASTRO), the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and the American Head & Neck Society (AHNS), the Multidisciplinary Head and Neck Cancers Symposium brings researchers and clinicians together to discuss advances in research and treatments for head and neck cancers. For more information about the meeting, visit: View Source

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 free radical levels caused by radiation therapy by rapidly converting superoxide free radical molecules to hydrogen peroxide and oxygen. Left untreated, elevated superoxide free radicals can damage noncancerous tissues and lead to debilitating side effects, including oral mucositis (OM), which can limit the antitumor efficacy of radiation therapy.

GC4419 is initially being studied for its ability to reduce the incidence, duration and severity of radiation and chemotherapy-induced OM in patients with head and neck cancer. As reported in December 2017, top-line results from Galera’s 223-patient, double blind, randomized, placebo-controlled Phase 2b clinical trial demonstrate GC4419’s ability to dramatically reduce the duration of severe OM from 19 days to 1.5 days (92 percent), the incidence of severe OM through completion of radiation by 34 percent and the severity of patients’ OM by 47 percent, while preserving healthy tissue. In addition, in preclinical study GC4419 demonstrated an increased tumor response to radiation therapy while preventing toxicity in normal tissue.

The U.S. Food and Drug Administration granted Fast Track designation to GC4419 for the reduction and incidence of radiotherapy induced OM in patients with head and neck cancer. GC4419 also has potential in other indications in which mucosa is damaged by radiation.

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.

On January 4, 2017 Rocket Pharmaceuticals, Ltd., a leading U.S.-based multi-platform gene therapy company addressing challenging rare diseases, reported the completion of its merger with Inotek Pharmaceuticals Corporation ("Inotek") (Press release, Rocket Pharmaceuticals, JAN 4, 2018, View Source [SID1234522921]). The combined company ("Company") will be named Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) ("Rocket") and will focus on advancing a pipeline of gene therapy programs targeting rare and undertreated diseases. Rocket’s common stock will be listed on the NASDAQ Global Market under the symbol "RCKT" and is expected to be begin trading on January 5, 2018. Rocket is based in New York City and led by President and Chief Executive Officer Gaurav Shah, M.D., who previously was a Global Program Head in the Cell & Gene Therapies Unit at Novartis.

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"The support for this transaction by both Inotek and Rocket shareholders was evident today, underscoring support for our long-term growth strategy to become a fully-integrated, multi-platform gene therapy company"

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"The support for this transaction by both Inotek and Rocket shareholders was evident today, underscoring support for our long-term growth strategy to become a fully-integrated, multi-platform gene therapy company," said Dr. Shah. "The closing of this merger provides immediate value to grow our operations, execute on our clinical development goals, and expand our in-house manufacturing and analytics capabilities. As we enter this next stage of growth as a publicly traded company, we are focused on driving Company value by bringing our current pipeline of five programs to major value inflection points as rapidly as possible, and achieving first mover advantage in these markets."

Rocket’s Pipeline

Rocket utilizes a multi-platform development approach that leverages the well-established lentiviral vector (LVV) and adeno-associated viral vector (AAV) gene delivery methods and is initially targeting devastating rare diseases in children that lead to early mortality in the absence of bone marrow transplant or other invasive procedures.

The Company’s lead program, a Phase 1/2 LVV-based gene therapy for Fanconi Anemia (FA), is currently in clinical trials with academic partners in the U.S. and Europe. FA causes genetic instability due to mutations in DNA repair genes resulting in early bone marrow failure and malignancy. Early results in FA patients have demonstrated clinical engraftment of ex vivo-transduced autologous hematopoietic stem cells (HSCs). The proportion of gene-corrected cells increases over time, confirming the selective advantage of gene-corrected cells in the bone marrow without requiring conditioning (i.e. destruction of bone marrow prior to transplant). Functional correction and clinical proof of concept have also been observed. Both blood and marrow cells demonstrate resistance to DNA-damaging agents (sensitivity to DNA-damaging agents is a diagnostic feature of FA). Patients demonstrated stable or improving blood cell counts during the months following treatment despite decreases noted during the months and years preceding gene therapy. Additional patient data are expected in 2018, with a registration study anticipated to start in 2019.

Three additional LVV-based programs are currently in preclinical development and target Leukocyte Adhesion Deficiency-I (LAD-I), Pyruvate Kinase Deficiency (PKD) and Infantile Malignant Osteopetrosis (IMO). The LAD-I program is expected to advance into the clinic in 2018, with the PKD and IMO programs to follow in 2019.

An undisclosed AAV-based gene therapy program is expected to enter the clinic in the next year and has demonstrated encouraging histological correction of the disease phenotype. This program targets a monogenic pediatric disease with early mortality and represents the first gene therapy being developed for this large class of indications.

Rocket’s Management

The combined Company’s executive management team will be led by Dr. Shah and will consist of: Jonathan Schwartz, M.D., Chief Medical Officer, who led several biologics approvals as Vice President of Clinical Development at ImClone Systems/Eli Lilly and Company; Kinnari Patel, Pharm.D., MBA, newly appointed Chief Operating Officer, who led regulatory filings for six rare disease agents as well as for Opdivo while at Bristol-Myers Squibb; and Brian Batchelder, MBA, Vice President of Finance, who previously served as Chief Financial Officer of ImClone Systems, a subsidiary of Eli Lilly and Company.

In addition, Rocket appointed Claudine Prowse, Ph.D., as Head of Corporate Development and Investor Relations Officer. Previously, she was Head of Strategy at Inotek, where she was integral to the merger transaction with Rocket Pharmaceuticals, Ltd. Prior to that, she was Vice President of Investor Relations at Biogen.

About the Merger

Prior to the closing of the merger, Inotek effected a 1 for 4 reverse split of its common stock. Following the reverse stock split and closing of the merger, there will be approximately 33.1 million shares of the combined company’s common stock outstanding with prior Rocket shareholders owning approximately 79.4% and prior Inotek shareholders owning approximately 20.6%. Based on the reverse stock split, the conversion rate of the combined Company’s $52.0 million of 5.75% Convertible Senior Notes due 2021 will automatically be adjusted from 124.7505 shares of common stock per $1,000 principal amount of the notes to 31.1876 shares of common stock per $1,000 principal amount of the notes. Cash, cash equivalents and short-term investments for the combined Company at closing were approximately $117.2 million.