On September 12, 2016 Galena Biopharma, Inc. (NASDAQ:GALE), a biopharmaceutical company committed to the development and commercialization of hematology and oncology therapeutics that address unmet medical needs, reported the issuance of a second Japanese Patent (JP Patent #5985719) containing composition and method of use claims for GALE-401, the Company’s controlled release version of anagrelide (Press release, Galena Biopharma, SEP 12, 2016, View Source [SID:SID1234515094]). The patent covers the treatment of patients suffering from myeloproliferative diseases, including myeloproliferative neoplasms (MPNs) such as essential thrombocythemia (ET) and polycythemia vera. The patent provides GALE-401 exclusivity until 2029, not including any patent term extensions.

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"With our plans to initiate a Phase 3 trial next year in essential thrombocythemia, we are looking to position GALE-401 as a potential treatment option for MPN patients worldwide," said Mark W. Schwartz, Ph.D., President and Chief Executive Officer. "This Japanese patent further expands our international intellectual property (IP) position complementing our IP estate in the United States. Branded anagrelide immediate release was approved in Japan in 2014.

GALE-401 contains the active ingredient anagrelide. The currently available immediate release formulation (Agrylin or anagrelide IR) is approved in the U.S., Europe and Japan for the treatment of patients with thrombocythemia, secondary to myeloproliferative disorders, to reduce the elevated platelet count and the risk of thrombosis, and to ameliorate associated symptoms including thrombo-hemorrhagic events. Adverse events associated with anagrelide IR, such as nausea, diarrhea, abdominal pain, palpitations, tachycardia, and headache, may be dose and plasma concentration dependent. GALE-401 is a controlled release formulation of anagrelide, which significantly reduces the maximum plasma concentration (Cmax), and is expected to reduce side effects, but preserve efficacy. A Phase 2 pilot study with GALE-401 has been completed and Galena expects to launch a Phase 3 trial in the first half of 2017.

About Myeloproliferative Neoplasms and Essential Thrombocythemia

Myeloproliferative neoplasms (MPNs) are a closely related group of progressive blood cancers in which the bone marrow typically overproduces one of the mature blood elements. Other shared features include tendencies toward blood clotting/bleeding, organ enlargement, bone marrow scarring (fibrosis) and a possibility of transformation. The main MPNs are polycythemia vera (PV), chronic myelogenous leukemia (CML), primary myelofibrosis (PMF), and essential thrombocythemia (ET), all of which are associated with high platelet counts. The MPNs are progressive blood cancers that can strike anyone at any age, and for which there is no known cure.

Thrombocythemia is a myeloproliferative blood disorder. It is characterized by the production of too many platelets in the bone marrow. Too many platelets make normal clotting of blood difficult. It can be either reactive or primary (also termed essential and caused by a myeloproliferative disease). Primary Thrombocytosis (essential thrombocythemia or ET) is due to a failure to regulate the production of platelets (autonomous production) and is a feature of a number of myeloproliferative disorders. About a third of patients are asymptomatic at the time of diagnosis.

On September 12, 2016 Rexahn Pharmaceuticals, Inc. (NYSE MKT:RNN), a clinical stage biopharmaceutical company developing next generation targeted therapeutics for the treatment of cancer, reported it has initiated stage 2 of the Phase Ib/IIa clinical trial with the novel oral anti-cancer agent RX-3117 in relapsed or refractory pancreatic cancer patients (Filing, 8-K, Rexahn, SEP 12, 2016, View Source [SID:SID1234515093]). The decision to proceed was based on satisfying the predefined criteria for preliminary efficacy for stage 1 of the trial. RX-3117 was safe and well tolerated with preliminary efficacy seen in pancreatic cancer patients for whom three prior therapies had been ineffective.

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"These data are very promising since there are no available treatments for pancreatic cancer patients who have failed three prior therapies. These patients would usually be offered palliative or best supportive care. Having 40% of patients showing responses beyond 2 months is certainly encouraging. I look forward to further evidence of benefit at the end of the trial," said Ely Benaim, M.D., Chief Medical Officer for Rexahn.

"The initiation of stage 2 of the Phase Ib/IIa clinical trial in refractory metastatic pancreatic cancer marks a major milestone in the RX-3117 clinical development program," commented Peter D. Suzdak, Ph.D., Chief Executive Officer. "Results from stage 1 of the Phase Ib/IIa clinical trial have been submitted for presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) conference that will take place in October 2016."

The ongoing Phase Ib/IIa clinical trial is a multicenter, open-label single-agent study of RX-3117 being conducted at 10 clinical centers in the United States. Patients receive a 700 mg daily oral dose of RX-3117, five times weekly on a three weeks on, one week off dosing schedule in a 28 day cycle for up to eight treatment cycles, or until their disease progresses. The study follows a two-stage design. In stage 1 of the trial, up to 10 patients with relapsed or refractory metastatic pancreatic cancer were enrolled. Based on predefined criteria, if 20% or more of the patients had progression free survival of > 4 months, or an objective clinical response rate and reduction in tumor size, then an additional 40 pancreatic cancer patients would be enrolled into stage 2.

Patients enrolled into stage 1 of the clinical trial had actively progressing disease, with 44% of them having failed > 3 prior cancer therapies (including 5-FU and gemcitabine-based therapies). RX-3117 was shown to be safe and well tolerated in this patient group. The clinical study is still on-going. However since the predefined efficacy criteria have been achieved, stage 2 of the study has been initiated.

About RX-3117

RX-3117 is a novel, investigational small molecule nucleoside compound. Once intracellularly activated (phosphorylated) by UCK2, it is incorporated into the DNA or RNA of cells and inhibits both DNA and RNA synthesis, which induces apoptotic cell death of tumor cells. UCK2 is highly overexpressed in various human cancer cells. Preclinical studies have shown that RX‑3117 has shown broad spectrum anti-tumor activity against over 100 different human cancer cell lines and efficacy in 17 different mouse xenograft models including pancreatic, bladder, lung, cervical and colon cancers, as well as gemcitabine resistant cancer cells. Importantly, RX-3117 still retains its full anti-tumor activity in human cancer cell lines made resistant to the anti-tumor effects of gemcitabine.

Rexahn has previously reported the completion of an exploratory Phase I clinical trial of RX-3117 in cancer patients conducted in Europe, to investigate the oral bioavailability, safety and tolerability of the compound. In this study, oral administration of a 50 mg dose of RX-3117 showed an oral bioavailability of 56% and a plasma half-life (T1/2) of 14 hours. In addition, RX-3117 appeared to be safe and well tolerated in all subjects throughout the dose range tested.

In June 2016, final results from the Phase Ib clinical trial of RX-3117 were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting showing encouraging evidence of the single agent activity. Patients in the study were heavily pre-treated, and had generally received four or more cancer therapies prior to enrollment. In this study, 12 patients experienced stable disease persisting for up to 276 days and three patients showed evidence of tumor burden reduction. A maximum tolerated dose of 700 mg was identified in the study and will be administered for five consecutive days, with two days off, for three treatment weeks, followed by a week of rest. At the doses tested to date, RX-3117, administered orally, appeared to be safe and well tolerated with a predictable pharmacokinetic profile for an orally-administered route of therapy.

Based on these data, Rexahn initiated a Phase Ib/IIa clinical trial of RX-3117 in patients with relapsed or refractory pancreatic cancer to further evaluate the safety and anti-cancer properties of this compound. The Phase Ib/IIa clinical trial is a multi-center study that will evaluate the safety and efficacy of RX-3117 in this target patient population. Secondary endpoints include safety and pharmacokinetic analyses. Patient enrollment has been initiated. Patients in the trial will be receiving a 700 mg daily oral dose of RX-3117, five times weekly for three weeks in a 28 day cycle for up to eight treatment cycles, or until their disease progresses. If > 20 % of the patients have an increase in progression free survival of > 4 months, or an objective clinical response rate and reduction in tumor size, then an additional 40 pancreatic cancer patients will be enrolled into stage 2. Secondary endpoints include time to disease progression, overall response rate and duration of response, as well as pharmacokinetic assessments and safety parameters.

Rexahn has received U.S. Food and Drug Administration (FDA) Orphan Drug Designation for RX-3117 for pancreatic cancer.

On September 12, 2016 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS), a clinical-stage company developing new therapeutics and molecular diagnostics that target the underlying mechanisms of cancer, reported that it has submitted a formal response to the U.S. Food and Drug Administration (FDA) regarding the previously announced clinical hold of Aptose’s Phase 1b clinical trial of APTO-253 in patients with hematologic cancers (Filing, 6-K, Aptose Biosciences, SEP 12, 2016, View Source [SID:SID1234515069]). Aptose provided responses to all of the questions cited in the clinical hold letter issued by the FDA.

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"This submission represents months of disciplined labor to resolve a manufacturing matter related to APTO-253 that arose during our Phase 1b Trial in patients with AML and high-risk MDS," commented Dr. William G. Rice, Chairman, President and Chief Executive Officer. "Although the FDA will make the ultimate decision whether our clinical trial may resume, all of their questions have been addressed."

During a Phase 1b clinical trial with APTO-253, a clinical site experienced stoppage of the infusion pump during an IV infusion caused by back pressure as a result of clogging of the in-line filter. The Company determined the root cause was a chemistry-based issue with the molecule, and the Company is now working with a drug product that does not cause filter clogging or pump stoppage during mock infusion studies performed to confirm the acceptability of the updated product through the clinical infusion procedures. Such improvements to the APTO-253 manufacturing process required to address the filter clogging event will be incorporated into a Chemistry, Manufacturing and Control (CMC) amendment to our Investigational New Drug application.

On September 12, 2016 Sunesis Pharmaceuticals, Inc. (Nasdaq:SNSS) reported results from the Company’s Phase 1A study in healthy volunteers evaluating oral non-covalent BTK inhibitor SNS-062 (Press release, Sunesis, SEP 12, 2016, View Source [SID:SID1234515068]). The study demonstrated a favorable safety, pharmacokinetic (PK) and pharmacodynamic (PD) profile for SNS-062 in healthy subjects. The results were presented on Saturday, September 10th at the European School of Haematology’s (ESH) 2nd International Conference on New Concepts in B-Cell Malignancies at the Estoril Congress Centre in Estoril, Portugal.

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"Our first-in-human clinical results are encouraging and reinforce our belief that SNS-062 has the potential to become an important new treatment option for patients with B-cell malignancies," said Linda Neuman, M.D., Vice President, Clinical Development of Sunesis. "Notably, SNS-062 exposure, even at the lowest dose of 50 mg, exceeded those reported for both ibrutinib and acalabrutinib at their respective recommended dose levels, suggesting that SNS-062 has improved PK properties. Furthermore, as a non-covalent BTK inhibitor with a distinct binding profile, SNS-062 may overcome the acquired resistance to ibrutinib and other covalent clinical-stage inhibitors resulting from a point mutation (C481S) in the BTK active site."

"The safety profile and the extent and duration of BTK inhibition by SNS-062 support the timely advancement of this program into cancer-directed studies," said Daniel Swisher, President and Chief Executive Officer of Sunesis. "We look forward to moving SNS-062 into a planned Phase 1B/2 study of patients with advanced B-cell malignancies."

The reported data from this Phase 1A randomized, double-blind, placebo-controlled, single-dose study are from four sequential cohorts of 8 subjects each who were randomly assigned to receive progressively higher single oral administrations of SNS-062 at doses of 50, 100, 200, and 300 mg (n=6 per cohort) or placebo (n=2 per cohort). An evaluation of the effects of food and CYP3A4 inhibition on the PK of SNS-062 is ongoing.

For the primary endpoint of safety, investigators were blinded to treatment arm for assessment of relatedness. Overall, AEs were reported for 8 (33%) subjects who received SNS-062 and for 3 (38%) subjects who received placebo. Treatment-related AEs were reported in 6/24 (25%) subjects who received SNS-062 compared with 3/8 (38%) subjects who received placebo. For patients who received SNS-062, treatment-related AEs included headache, nausea, and supraventricular tachycardia. In the placebo group, treatment-related AEs included headache, nausea, and diarrhea. No obvious pattern of dose-dependent toxicity was observed. All AEs were transient and low grade. None of the AEs, laboratory abnormalities, or ECG or telemetry findings were considered clinically meaningful. No SAEs were reported.

SNS-062 was rapidly absorbed and had mean plasma half-life values across all dose cohorts of 7.4 to 17 hours. SNS-062 concentrations declined in a multiphasic manner. Total exposure (AUC and Cmax) increased proportionally with dose. SNS-062 demonstrated rapid, profound (~100%), and prolonged inhibition of BTK at all dose levels supporting a future twice-daily dosing regimen.

The poster, titled "A Phase 1A Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of the Noncovalent Bruton Tyrosine Kinase (BTK) Inhibitor SNS-062 in Healthy Subjects: Preliminary Results" is available on the Sunesis website at www.sunesis.com.

About SNS-062
SNS-062 is a novel, second-generation BTK inhibitor, a class of kinase inhibitors that selectively inhibits the enzyme Bruton’s tyrosine kinase (BTK). This target mediates signaling through the B-cell receptor, which is critical for adhesion, migration, proliferation and survival of normal and malignant B-lineage lymphoid cells. SNS-062’s favorable safety, pharmacokinetics, potency, kinase selectivity and non-covalent binding profile support the advancement to a Phase 1B/2 study in patients with B-cell malignancies. This study will include patients with an acquired resistance from a C481S mutation at the point in the enzyme’s binding site required for covalent binding of ibrutinib and other covalent inhibitors.

On September 12, 2016 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to niraparib for the treatment of patients with recurrent platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer (Press release, TESARO, SEP 12, 2016, View Source [SID:SID1234515067]). TESARO has initiated a rolling submission of a New Drug Application (NDA) for niraparib to the FDA, and intends to complete this submission during the fourth quarter. The Marketing Authorization Application (MAA) for niraparib is planned for submission to the European Medicines Agency (EMA) in the fourth quarter.

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The FDA Fast Track designation is designed to facilitate the development and expedite the review of medicines that are intended to treat serious conditions and address unmet medical needs. As part of the Fast Track program, the FDA allows for the submission of completed portions of an NDA on an ongoing or rolling basis.

"The initiation of this rolling NDA submission is a significant milestone for TESARO, and we are committed to working collaboratively with the FDA to advance the review of the niraparib application," said Mary Lynne Hedley, Ph.D., President and COO of TESARO. "We look forward to presentation of data from the Phase 3 NOVA trial of niraparib in a Presidential Symposium session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) congress on October 8."

NOVA is a double-blind, placebo-controlled, international Phase 3 trial of niraparib that enrolled more than 500 patients with recurrent ovarian cancer who were in a response to their most recent platinum-based chemotherapy.

About Niraparib
Niraparib is an oral, once-daily PARP inhibitor that is currently being evaluated in four ongoing pivotal trials. TESARO is building a robust niraparib franchise by assessing activity across multiple tumor types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development program for niraparib includes a Phase 3 trial in patients with platinum-sensitive, recurrent ovarian cancer (the NOVA trial); a Phase 3 trial in patients with first-line ovarian cancer (the PRIMA trial); a registrational Phase 2 treatment trial in patients with ovarian cancer (the QUADRA trial); and a Phase 3 trial for the treatment of patients with BRCA-positive breast cancer (the BRAVO trial). Several combination studies are also underway, including trials of niraparib plus pembrolizumab and bevacizumab.

Niraparib is an investigational agent and, as such, has not been approved by the U.S. FDA or any other regulatory agencies.