On December 19, 2018 On December 19, 2018, BeiGene, Ltd. (the "Company") reported that it received notice from Merck KGaA ("Merck KGaA") that Merck KGaA was terminating for convenience the parties’ License Agreement dated December 10, 2013, as amended, for the Company’s investigational RAF dimer inhibitor lifirafenib (BGB-283) in the People’s Republic of China ("PRC") (Filing, 8-K, BeiGene, DEC 19, 2018, View Source [SID1234532301]). As a result of such termination, Merck KGaA’s exclusive right of first negotiation to acquire exclusive commercialization rights under the lifirafenib RAF dimer program in the PRC was terminated and the Company is no longer required to pay Merck KGaA royalties on sales of lifirafenib in the PRC or entitled to receive future milestone payments from Merck KGaA for lifirafenib. The Company’s ex-PRC agreement with Merck KGaA on lifirafenib was terminated in March 2017.

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On December 19, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that the first patient has been dosed in the first novel-novel combination study evaluating two investigational agents within its AML Franchise (Press release, Daiichi Sankyo, DEC 19, 2018, View Source [SID1234532207]). The phase 1 study will evaluate the safety and activity of the combination of a FLT3 inhibitor, quizartinib, and an MDM2 inhibitor, milademetan (DS-3032), in patients with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML) or newly-diagnosed FLT3-ITD AML unfit for intensive chemotherapy, a very aggressive form of the disease associated with poor prognosis.

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"We have initiated this combination study of quizartinib and milademetan in order to determine the safety and tolerability of the combination and if the addition of the MDM2 inhibitor milademetan may potentially further improve the outcomes of patients with relapsed/refractory FLT3-ITD AML beyond what has been previously reported with single agent quizartinib," said Arnaud Lesegretain, Vice President, Oncology R&D and Head, AML Franchise, Daiichi Sankyo. "In this study, we also are exploring the potential of the combination of quizartinib and milademetan in patients with newly-diagnosed FLT3-ITD AML who are unfit for intensive chemotherapy. This study is the first of several planned studies that will evaluate the potential of novel combinations within our investigational AML Franchise, as we are committed to continuously improving the standard of care for patients with AML."

Quizartinib is the first FLT3 inhibitor to demonstrate a survival benefit as an oral, single agent compared to chemotherapy in a randomized, phase 3 study (QuANTUM-R) in patients with FLT3-ITD AML, which was refractory or relapsed within six months of first remission, and single agent milademetan has demonstrated preliminary clinical activity in AML and myelodysplastic syndrome (MDS) in a phase 1 study.1,2 Additionally, preclinical research has shown that the combination of quizartinib and milademetan has greater activity in FLT3-ITD AML cells compared to the respective single agent treatments.3

In the QuANTUM-R study, the median treatment duration with quizartinib was 4 cycles of 28 days each versus 1 cycle in the salvage chemotherapy arm. Incidence of treatment-emergent adverse events was comparable between patients who received single agent quizartinib and those who received salvage chemotherapy. The most common adverse drug reactions (>30 percent, any Grade) in patients treated with quizartinib included infections, bleeding, nausea, asthenic conditions, pyrexia, febrile neutropenia and vomiting, and the most common Grade ≥ 3 adverse drug reactions (>20 percent) were infection and febrile neutropenia. The most common laboratory adverse reactions (incidence >50 percent) were decreased white blood cell count, decreased lymphocyte count, decreased hemoglobin, decreased neutrophil count and decreased platelet count. The safety profile observed in QuANTUM-R appears consistent with that observed at similar doses in the quizartinib clinical development program.

In addition to the quizartinib and milademetan combination study, an ongoing phase 1 study of milademetan has been expanded to include evaluation of milademetan in combination with the hypomethylating agent 5-azacitidine, an inhibitor of DNA methylation, in patients with newly-diagnosed AML unfit for intensive chemotherapy, relapsed/refractory AML or high-risk MDS.

About the Quizartinib/Milademetan Combination Study

The multi-center, non-randomized, phase 1, open-label, two-part study is investigating the safety and efficacy of the combination of quizartinib and milademetan in patients with relapsed/refractory FLT3-ITD AML or newly-diagnosed FLT3-ITD AML unfit for intensive chemotherapy. The first part of the study (dose escalation) will assess the safety and tolerability of the combination to determine the dosing schedule, maximum tolerated dose and recommended dose for expansion. The second part of the study (dose expansion) will confirm the safety and tolerability at the recommended dose for expansion of the combination and will identify a recommended phase 2 dose. The primary objective of the study is safety. Secondary objectives include evaluation of pharmacokinetics and preliminary efficacy. The study is expected to enroll approximately 110 patients in the U.S., EU and Japan. For more information about the study, visit ClinicalTrials.gov.

About the Milademetan/5-Azacitidine Combination Study

The multi-center, non-randomized, phase 1, open-label, two-part study is investigating the safety and efficacy of milademetan as a single agent and in combination with the hypomethylating agent 5-azacitidine. The first part of the study (dose escalation) will evaluate the safety and tolerability and identify the maximum tolerated dose and recommended dose for expansion of milademetan as a single agent and in combination with 5-azacitidine in patients with relapsed/refractory AML or high-risk MDS. The second part of the study (dose expansion) will confirm the safety and tolerability at the recommended dose of milademetan in combination with 5-azacitidine and will identify a recommended phase 2 dose in patients with relapsed/refractory AML, newly-diagnosed AML unfit for intensive chemotherapy or high-risk MDS. The primary objectives of the study are safety and tolerability, maximum tolerated dose, recommended dose for expansion and response to treatment. Key secondary objectives include evaluation of pharmacokinetics and pharmacodynamic effects. The study is expected to enroll up to 200 patients in the U.S. For more information about the study, visit ClinicalTrials.gov.

About Acute Myeloid Leukemia and Myelodysplastic Syndrome

AML is an aggressive blood and bone marrow cancer that causes uncontrolled growth and accumulation of malignant white blood cells that fail to function normally and interfere with the production of normal blood cells.4 In the U.S. this year, it is estimated that there will be more than 19,000 new diagnoses of AML and more than 10,000 deaths from AML.5 The five-year survival rate of AML reported from 2007 to 2013 was approximately 27 percent, which was the lowest of all leukemias.4

FLT3 gene mutations are one of the most common genetic abnormalities in AML.6 FLT3-ITD is the most common FLT3 mutation, affecting approximately one in four patients with AML.7,8,9,10 FLT3-ITD is a driver mutation that presents with high leukemic burden and has poor prognosis and a significant impact on disease management for patients with AML.8,11 Patients with FLT3-ITD AML have a worse overall prognosis, including an increased incidence of relapse, an increased risk of death following relapse and a higher likelihood of relapse following hematopoietic stem cell transplantation as compared to those without this mutation.12,13

MDS is a type of cancer that can occur when blood-forming cells in the bone marrow become abnormal.14 There were over 14,000 new cases of MDS diagnosed each year from 2010 to 2014.4 In about one in three patients, MDS progresses to AML.14

About Quizartinib

Quizartinib, the lead investigational agent in the AML Franchise of the Daiichi Sankyo Cancer Enterprise, is an oral selective type II FLT3 inhibitor currently in phase 3 development for relapsed/refractory FLT3-ITD AML (QuANTUM-R) in the U.S. and EU; phase 3 development for newly-diagnosed FLT3-ITD AML (QuANTUM-First) in the U.S., EU and Japan; phase 2 development for relapsed/refractory FLT3-ITD AML in Japan; and phase 1 development in combination with an investigational agent, milademetan, for relapsed/refractory FLT3-ITD AML and newly-diagnosed FLT3-ITD AML unfit for intensive chemotherapy in the U.S., EU and Japan.

Quizartinib has been granted Priority Review and Breakthrough Therapy designation for the treatment of adult patients with relapsed/refractory FLT3-ITD AML, and Fast Track designation for the treatment of relapsed/refractory AML by the U.S. Food and Drug Administration (FDA). Quizartinib also has been granted accelerated assessment by the European Medicines Agency (EMA) for the treatment of adults with relapsed or refractory AML, which is FLT3-ITD positive, and granted Orphan Drug designation by both the FDA and the European Commission (EC) for the treatment of AML and by the Japan Ministry of Health, Labour and Welfare (MHLW) for the treatment of FLT3-mutated AML.

About Milademetan

Milademetan (DS-3032) is an oral selective MDM2 inhibitor currently in phase 1 clinical development for solid and hematologic malignancies, including a combination study with quizartinib in relapsed/refractory FLT3-ITD AML or newly-diagnosed FLT3-ITD AML unfit for intensive chemotherapy in the U.S., EU and Japan; a single agent and combination study with 5-azacitidine in newly-diagnosed AML unfit for intensive chemotherapy, relapsed/refractory AML or high-risk MDS in the U.S.; and two single agent studies in lymphomas and solid tumors in the U.S. and Japan.

Quizartinib and milademetan are investigational agents that have not been approved for any indication in any country. Safety and efficacy of these investigational agents have not been established.

On December 19, 2018 MannKind Corporation (Nasdaq: MNKD) (MannKind) reported the pricing of an underwritten public offering of 26,666,667 shares of its common stock and warrants to purchase up to an aggregate of 26,666,667 shares of its common stock (Press release, Mannkind, DEC 19, 2018, View Source [SID1234532189]). Each share of common stock is being sold together with a warrant to purchase one share of common stock for a combined purchase price of $1.50, for a gross deal size of $40.0 million, not including any future proceeds from the exercise of the warrants and before deducting the underwriting discounts and commissions and offering expenses. Each warrant will have an exercise price of $1.60 per share, will be exercisable immediately and will expire on the 12-month anniversary of the date of issuance. The shares of common stock and warrants can only be purchased together but will be issued separately and will be immediately separable upon issuance. The offering is expected to close on December 26, 2018, subject to customary closing conditions.

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Leerink Partners is acting as sole book-running manager for the offering. BTIG, LLC and Oppenheimer & Co. Inc. are acting as co-lead managers for the offering. H.C. Wainwright & Co., LLC acted as a financial advisor to MannKind in connection with the offering.

The securities described above are being offered by MannKind pursuant to a shelf registration statement on Form S-3 (No. 333-210792) previously filed by MannKind with the Securities and Exchange Commission (SEC) on April 18, 2016 and declared effective on April 27, 2016. The offering will be made only by means of a written prospectus and prospectus supplement that form part of the registration statement. A preliminary prospectus supplement related to the offering and accompanying prospectus has been filed with the SEC and is available on the SEC website located at View Source Copies of the final prospectus supplement and the accompanying prospectus related to the offering, when available, may be obtained from Leerink Partners LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, telephone: (800) 808-7525, ext. 6132, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of any securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On December 19, 2018 Medigene AG (FWB: MDG1, Prime Standard, SDAX) reported interim clinical results from its ongoing company-sponsored Phase I/II clinical trial of a dendritic cell (DC) vaccine in 20 patients with acute myeloid leukemia (AML) (Press release, MediGene, DEC 19, 2018, View Source [SID1234532188]). The primary objectives of the study are the safety and feasibility of this active immunotherapy with the patient-derived DCs produced according to Medigene’s proprietary technology.

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The topline data released today is from a period of one year of vaccination of all patients and represents an interim dataset after half of the treatment period.

A total of 20 subjects (median age 59, range 24 to 73) with AML (risk groups good, intermediate, poor: 13, 5, 2), in morphologic complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) after induction or consolidation therapy, not eligible for allogeneic hematopoietic stem cell transplantation, were enrolled into this safety and feasibility Phase I/II trial, vaccinated and followed up for 12 months. Subjects in this trial had AML that was positive for Wilms Tumor-1 (WT-1) antigen with or without positivity for Preferentially Expressed Antigen in Melanoma (PRAME). Vaccination with dendritic cells, presenting the antigens WT-1 and PRAME, was carried out monthly, with a higher frequency within the first 6 weeks. AML diagnoses had been established with a median of 9.8 months before the first vaccination (range 4.5 to 17.5 months), and the last chemotherapy infusion had been performed at a median of 6.9 months (range 2 to 14.8 months).

The vaccinations were well tolerated with no serious adverse events (SAEs) related to the treatment. The most common adverse events (AEs) were injection site related, accounting for 35% of all AEs and mild in nature (Grade 1). The feasibility of the manufacture of the dendritic cell vaccine in these chemotherapy-pretreated subjects was already presented earlier this year (abstract AACR (Free AACR Whitepaper)). Link to poster: View Source

After a 12-months treatment period, the overall survival was 89% (18 of 20 patients, 95% confidence interval: 61 to 97%) and the progression free survival was 60% (12 of 20 patients, 95% confidence interval: 36 to 78%). Most relapses, 5 out of 8, occurred within the first 80 days after the start of the vaccination, out of which the 2 deaths were in patients with relapses on days 45 and 64, which could point to a starting relapse upon entering the study.

The completion of the ongoing trial is scheduled for the end of 2019 following a two-year treatment period.

Dr. Yngvar Floisand, Head Physician of the Department of Hematology at the Oslo University Hospital and Principal Investigator of the trial, comments: "The interim results after one year of treatment demonstrate an excellent safety profile and a very good manufacturability of Medigene’s personalized DC vaccines. The initial data on the efficacy of the therapy point in the right direction, but we have to complete the two-year trial period for a conclusive evaluation."

Dr. Kai Pinkernell, CMO and CDO of Medigene AG, comments: "We are pleased about these first encouraging interim results from our ongoing safety and feasibility trial with our DC vaccine. AML is a serious disease with poor long-term prognosis and we are committed to developing new treatment options for those patients in urgent need."

Medigene intends to present the detailed data from the interim analysis at a scientific conference in the near future.

About acute myeloid leukaemia (AML): Acute myeloid leukaemia is a malignant disease of the hematopoietic system, affecting mainly adults above 60 years of age. In Germany, about 3,600 cases are registered annually.

AML is caused by uncontrolled growth of dysfunctional hematopoietic precursor cells in the bone marrow. These cells prevent the generation of normal blood cells, causing a decrease in erythrocytes and platelets, for example. Typical symptoms of AML include anemia, fever, increased risk of infection, and bleeding. AML progresses rapidly and may be fatal within a few weeks or months, if untreated.

AML treatment is often started with intensive chemotherapy, followed by consolidation with or without allogeneic hematopoietic stem cell transplantation. Unfortunately, a significant proportion of patients suffer a relapse of the original disease. Depending on the biologic risk profile of the disease, age and co-morbidity the long-term survival is highly variable.

About Medigene’s DC vaccines: In addition to Medigene’s development focus on T cell-receptor modified T cells (TCR-Ts), the Company has developed a new generation of antigen-tailored dendritic cell (DC) vaccines.

Dendritic cells (DC) can take up antigens, process them and present peptides on their surface in a form that can induce antigen-specific T cells to mature and proliferate. In this way, T cells recognize and eliminate tumor cells which bear the same antigen peptide on their surface. Dendritic cells can also induce natural killer cells (NK cells) to attack tumor cells. The scientific team of Medigene has developed new, fast and efficient methods for generating autologous (patient-specific) mature dendritic cells which have the relevant characteristics to generate very strong T cell and NK cell immune responses. The dendritic cells can be loaded with various tumor antigens to treat different forms of cancer. Since an immune response builds up over the total time of administration of the DC vaccine, this form of therapy is particularly designed for patients who suffer from a tumor disease which has been reduced to such an extent by chemotherapy that the prevention of the recurrence of the tumor disease is the main goal

On December 19, 2018 Applied DNA Sciences, Inc. (Nasdaq: APDN) ("Applied DNA" or the "Company"), a leader in large-scale PCR-based DNA manufacturing, reported that it intends to offer for sale a combination of shares of its common stock and warrants to purchase shares of its common stock in an underwritten public offering (Press release, Applied DNA Sciences, DEC 19, 2018, View Source [SID1234532183]). The Company intends to use the net proceeds from this offering for working capital, capital expenditures, business development and research and development expenditures. The offering is subject to market conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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Maxim Group LLC is acting as sole underwriter and book-running manager for the offering.

The securities described above are being offered under the Company’s shelf registration statement on Form S-3 (No. 333-218158), previously filed with and declared effective by the U.S. Securities and Exchange Commission (SEC). The securities will be offered by means of a prospectus supplement and accompanying prospectus, forming a part of the effective registration statement. The prospectus supplement and accompanying prospectus related to the offering will be filed with the SEC and will be available on the website of the SEC at View Source Electronic copies of the prospectus supplement and accompanying prospectus also may be obtained from Maxim Group LLC, 405 Lexington Avenue, 2nd Floor, New York, NY 10174, at 212-895-3745. Before you invest, you should read the prospectus supplement and the accompanying prospectus in the registration statement and other documents Applied DNA has filed or will file with the SEC for more complete information about Applied DNA and the offering.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any offer or sale of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such jurisdiction.