On September 12, 2016 the biotech company MOLOGEN AG (ISIN DE0006637200; Frankfurt Stock Exchange Prime Standard: MGN) reported first preliminary data on its EnanDIM technology in a murine tumor model. EnanDIM is a new family of TLR9 agonists and so-called Immune Surveillance Reactivators (ISR) (Press release, Mologen, SEP 12, 2016, View Source [SID:SID1234515097]). The pre-clinical in vivo data shows that EnanDIM can reduce tumor growth and thus prolong survival. It has been shown previously that EnanDIM molecules broadly activate immune cells in vitro and revealed no signs of toxicity after the administration of maximal feasible doses in vivo. These data constitute the next pre-clinical step towards a clinical development program of EnanDIM in the treatment of cancer.

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"This is the next important step for our promising new generation TLR9 agonist EnanDIM. For the first time we observed reduced tumor growth in a murine model. These results strongly support the pre-clinical development of our EnanDIM compounds", said Dr Mariola Söhngen, CEO of MOLOGEN AG.

MOLOGEN’s new strategy program "Next Level", presented beginning of June 2016, includes a clear concentration on the lead product, the cancer immunotherapy lefitolimod and next-generation molecules EnanDIM.

EnanDIM (Enantiomeric, DNA-based, ImmunoModulator), as a new generation of immunomodulators and so-called Immune Surveillance Reactivators (ISR), belongs to the class of TLR9 agonists and represents one of MOLOGEN’s follow-up compounds to lefitolimod (MGN1703) exhibiting longer patent protection, and a one-step production process as well as an immunomodulatory pattern dependent on the specific EnanDIM molecule.

The EnanDIM molecules consist entirely of natural DNA, as is also the case with lefitolimod (MGN1703). The main difference between MOLOGEN’s two ISR families is their molecule structure. Whereas lefitolimod (MGN1703) is dumbbell-shaped and covalently-closed, EnanDIM molecules have a linear structure. However, as with lefitolimod (MGN1703), due to its specific structure, no chemical modification is needed in order to protect the molecules against degradation by enzymes.

The EnanDIM ISR promise a broad activation of the immune system with a good safety and tolerability profile. Due to their characteristic mechanism of action, EnanDIM molecules have the potential to be applied in various cancer indications. Additionally, it may be possible to develop selected members of the EnanDIM family both for monotherapy and in combination with targeted forms of treatment, such as checkpoint inhibitors and other immunotherapeutic approaches. Moreover, different members of the EnanDIM family may also be used in the area of infectious diseases – including HIV.

The data will be presented at the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) in New York, USA (September 25-28, 2016). The conference will be organized by the Cancer Research Institute (CRI), die Association for Cancer lmmunotherapy (CIMT) (Free CIMT Whitepaper), the European Academy of Tumor Immunology (EATI), and the American Association for Cancer Research (AACR) (Free AACR Whitepaper).

Abstract details:

Abstract number: # 278

Title: "Preclinical data of novel enantiomeric oligonucleotides for cancer immunotherapy: The TLR9 agonist EnanDIM"

Poster presentation: September 26, from 5:15-7:45 pm

Poster Number: B067

For more information on the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) please visit the website: www.aacr.org.

About EnanDIM

EnanDIM (Enantiomeric, DNA-based, ImmunoModulator) is an innovative linear DNA-based TLR9 agonist in pre-clinical development. It broadly and strongly activates the immune system. EnanDIM could be used in various cancer indications either as monotherapy, in combination with other targeted therapies or immune modulators, such as so called checkpoint inhibitors, or with other immunotherapeutic approaches. It could also potentially be used in the field of infectious diseases.

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.