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Genmab Announces Net Sales of DARZALEX® (daratumumab) for First Quarter of 2018

On April 17, 2018 Genmab A/S (Nasdaq Copenhagen: GEN) reported that worldwide net sales of DARZALEX (daratumumab) as reported by Johnson & Johnson were USD 432 million in the first quarter of 2018 (Press release, Genmab, APR 17, 2018, View Source [SID1234525439]). Net sales were USD 264 million in the U.S. and USD 168 million in the rest of the world. Genmab will receive royalties on the worldwide net sales of DARZALEX under the exclusive worldwide license to Janssen Biotech, Inc. to develop, manufacture and commercialize DARZALEX.

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About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.1 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market. For more information, visit www.DARZALEX.com.
Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).1,2,3,4,5

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and frontline multiple myeloma settings and in amyloidosis. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases, such as NKT-cell lymphoma, myelodysplastic syndromes, B and T-ALL and selected solid tumors. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapies.. Net sales were USD 264 million in the U.S. and USD 168 million in the rest of the world. Genmab will receive royalties on the worldwide net sales of DARZALEX under the exclusive worldwide license to Janssen Biotech, Inc. to develop, manufacture and commercialize DARZALEX.

DelMar Pharmaceuticals Presents Positive Updates on Two Ongoing Clinical Trials with VAL-083 for Treatment of MGMT-unmethylated GBM

On April 17, 2018 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 Company presented a positive update on its two ongoing clinical trials of VAL-083, a first-in-class small molecule chemotherapeutic, for the treatment of MGMT-unmethylated Glioblastoma Multiforme ("GBM") at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") Annual Meeting (Press release, DelMar Pharmaceuticals, APR 17, 2018, View Source [SID1234525438]).

"We are pleased with the continued progress of our ongoing clinical trials with VAL-083 as a potential treatment for MGMT-unmethylated GBM," said Saiid Zarrabian, interim president and chief executive officer. "These trials are important elements of our clinical development strategy to advance VAL-083 as a potential treatment for GBM patients who have little or no viable alternatives."
DelMar presented the following updates in two poster presentations at the AACR (Free AACR Whitepaper) Annual Meeting.
1. A biomarker-driven, Phase 2 clinical trial of VAL-083 in patients with MGMT-unmethylated bevacizumab (Avastin)-naïve recurrent glioblastoma, currently being conducted in collaboration with the University of Texas MD Anderson Cancer Center.

Up to 48 patients with MGMT-unmethylated, bevacizumab-naïve, recurrent GBM, will be enrolled to determine if treatment with VAL-083 improves overall survival compared to historical reference control.
22 of a planned 48 patients have been enrolled as of March 31, 2018, compared to 15 patients enrolled as of October 31, 2017.

7 of the 22 enrolled patients (32%) have exhibited stable disease as best response.
Similar to prior clinical experience, myelosuppression has been the most common adverse event observed.
2. A Phase 1-2 clinical trial of VAL-083 in combination with radiotherapy in patients with newly diagnosed MGMT-unmethylated GBM, currently being conducted in collaboration with Sun Yat-sen University Cancer Center.
Up to 30 patients with newly diagnosed MGMT-unmethylated GBM will be treated with VAL-083 combined with radiotherapy by 24 weeks of VAL-083 maintenance therapy. The study is being conducted in two parts: (1) Dose-confirmation: VAL-083 in cohorts (20, 30 and 40 mg/m2/day IV) to assess safety and activity when administered concurrently with x-ray telescope ("XRT") to confirm the maximum tolerated dose ("MTD"), and (2) Expansion: VAL-083 will be studied in up to 20 additional patients at the target dose of 40mg/m2 VAL-083 administered concurrently with XRT.

Dose-confirmation studying 20 and 30 mg/m2/day cycles has been completed (4 patients enrolled).
No dose-limiting toxicities have been reported following treatment with multiple cycles of VAL-083.
The next patient enrolled will receive the study target dose of 40 mg/m2/day VAL-083 combined with radiation.
DelMar’s poster presentations can be viewed on the company’s website at:
View Source

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. VAL-083 has been granted fast-track status for the treatment of recurrent GBM by the US FDA.

Preclinical Data Demonstrate That Deciphera Pharmaceuticals’ DCC-2618 Exhibits Broader Inhibition Profile Against Primary and Secondary Drug-Resistant Mutations in Gastrointestinal Stromal Tumors (GIST) Compared to Approved and Investigational Agents

On April 17, 2018 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), a clinical-stage biopharmaceutical company focused on addressing key mechanisms of tumor drug resistance, reported pre-clinical data for DCC-2618 confirming a broad spectrum of potent inhibition across primary and secondary KIT mutations and primary PDGFRα mutations (Press release, Deciphera Pharmaceuticals, APR 17, 2018, View Source [SID1234525437]). Compared to the FDA approved and investigational compounds tested in this pre-clinical study, DCC-2618 demonstrated the broadest profile of inhibition of primary and secondary KIT mutations and primary PDGFRα mutations. The data will be presented today at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, IL in a poster titled "Inhibition of oncogenic and drug-resistant PDGFRA and KIT alterations by DCC-2618".

Deciphera is currently evaluating DCC-2618 in multiple clinical studies including INVICTUS, a Phase 3 pivotal study in 4th line and 4th line plus GIST patients, and in a Phase 1 study in other KIT and/or PDGFRα-driven diseases, including 2nd line to 4th line plus GIST, SM, glioblastoma multiforme and other cancers. Deciphera expects to initiate a Phase 3 registration study in 2nd line GIST patients in the second half of 2018 and to report top-line data from the ongoing INVICTUS study in 2019.

"In GIST patients receiving FDA approved therapies, secondary drug resistance KIT mutations frequently result in disease progression. Our pre-clinical results confirm that among the kinase inhibitors tested, both approved and investigational, DCC-2618 exhibits the broadest profile of inhibition against these heterogenous, difficult to treat mutations," said Michael D. Taylor, Ph.D., Deciphera’s President and Chief Executive Officer. "A significant need exists for therapies with the potential to address both activating mutations and other genetic alterations in KIT and PDGFRα, which have been identified in >85% of patients with GIST and >90% of patients with systemic mastocytosis."

These data describe the breadth of inhibition achieved with DCC-2618 and its active metabolite, DP-5439, across both primary and secondary KIT mutations and primary PDGFRα mutations compared to the in vitro profiles of the FDA-approved kinase inhibitors, imatinib, sunitinib, regorafenib, midostaurin and the investigational agent, avapritinib (BLU-285). Highlights from the poster include:

DCC-2618, a Type II switch control kinase inhibitor of KIT and PDGFRα, broadly inhibits KIT mutants in exons 9, 11, 13, 14 17, and 18 and PDGFRα mutants in exons 12, 14, and 18, forcing even aggressively activated kinase mutants into a Type II inactive conformation.

Compared to the approved and investigational compounds tested, DCC-2618 and its active metabolite, DP-5439, exhibit the broadest profile of inhibition across primary and secondary drug-resistant KIT mutations, and primary PDGFRα mutations.

Other Type II inhibitors, such as imatinib, sunitinib and regorafenib, do not broadly inhibit KIT exon-17 mutations or mutations in PDGRFα while Type I inhibitors, such as avapritinib (BLU-285), have weaker activity against KIT mutations in exons 13 and 14.

DCC-2618 also exhibited a superior exon 9 KIT mutation profile compared to imatinib, sunitinib, and avapritinib (BLU-285), including complex KIT mutations involving exon 9 coupled with secondary KIT mutations in exons 13, 14, and 17.

In enzyme assays at relevant cellular levels of adenosine triphosphate (ATP), DCC-2618 broadly inhibited primary and drug-resistant KIT mutants and primary PDGFRα mutants. DCC-2618 also broadly inhibited KIT and PDGFRα mutations in a panel of GIST, mastocytosis, leukemia, lung cancer, and transfected cell assays, as well as in various in vivo xenograft models.

As previously reported, translational liquid biopsy data from the Phase 1 clinical trial has shown that in heavily pre-treated GIST patients, many of whom had received all three of the FDA approved drugs for GIST, DCC-2618 decreased mutant KIT circulating tumor DNA (ctDNA) across the spectrum of KIT exons 9, 11, 13, 14, 17, and 18.

About DCC-2618
DCC-2618 is a KIT and PDGFRα kinase switch control inhibitor in clinical development for the treatment of KIT and/or PDGFRα-driven cancers, including gastrointestinal stromal tumors, systemic mastocytosis and glioblastoma multiforme. DCC-2618 was specifically designed to improve the treatment of GIST patients by inhibiting a broad spectrum of mutations in KIT and PDGFRα. DCC-2618 is a KIT and PDGFRα inhibitor that blocks initiating KIT mutations in exons 9, 11, 13, 14, 17, and 18, involved in GIST as well as the primary D816V exon 17 mutation involved in SM. DCC-2618 also inhibits primary PDGFRα mutations in exons 12, 14,and 18, including the exon 18 D842V mutation, involved in a subset of GIST.

Cellectar Presents Preclinical Data at AACR Annual Meeting Demonstrating Efficacy of Fractionated Injections of CLR 131 in Multiple Myeloma

On April 17, 2018 Cellectar Biosciences (Nasdaq: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported the presentation of a poster entitled "Efficacy of fractionated injections of CLR 131 in an OPM-2 mouse model" at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting underway in Chicago (Press release, Cellectar Biosciences, APR 17, 2018, View Source [SID1234525436]). Jarrod Longcor, chief business officer at Cellectar Biosciences, will conduct the presentation today, from 1:00 pm – 5:00 pm (CT), poster section 43.

The purpose of the study described in the poster was to evaluate the efficacy of fractionated CLR 131 in an OPM-2 multiple myeloma (MM) mouse model. A statistically significant reduction in tumor volume and an increase in overall survival was observed when mice were given 50uCi of CLR 131 once weekly for 2 weeks compared to all three active comparators in the study; a bortezomib arm dosed 0.6mg/kg twice weekly for two weeks and two single dose cohorts of CLR 131 (50 and 100uCi). The bortezomib dose has been previously shown to be efficacious in this MM model. Additionally, the time it took for tumors to double in size was markedly increased using fractionated dosing in comparison to the other treatments. Moreover, this dosing regimen showed improved tolerability as measured by body weight changes versus a single equivalent bolus dose further supporting the company’s plans to explore fractionated injections of CLR 131 in human clinical trials.

"The results seen in this study are promising because they demonstrate improved outcomes with fractionated injections vs single administration of CLR 131 in an established multiple myeloma animal model," said James Caruso, chief executive officer of Cellectar Biosciences. "We continue to see promise in CLR 131’s ability to demonstrate selective uptake and retention by malignant cells, while minimizing impact on healthy cells."

About CLR 131
CLR 131 is Cellectar’s investigational radioiodinated PDC therapy that exploits the tumor-targeting properties of the company’s proprietary phospholipid ether (PLE) and PLE analogs to selectively deliver radiation to malignant tumor cells, thus minimizing radiation exposure to normal tissues. CLR 131, is in a Phase 2 clinical study in relapsed or refractory (R/R) MM and a range of B-cell malignancies and a Phase 1 clinical study in patients with (R/R) MM exploring fractionated dosing. In 2018 the company plans to initiate a Phase 1 study with CLR 131 in pediatric solid tumors and lymphoma, and a second Phase 1 study in combination with external beam radiation for head and neck cancer.

AACR Meeting Brief: H3 Biomedicine, Checkmate, Deciphera and More

The following is a roundup of presentations and findings from multiple companies participating in the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) in Chicago (Press release, BioSpace, APR 17, 2018, View Source [SID1234525435]).

H3 Biomedicine Inc. – Working with Foundation Medicine, H3 Biomedicine unveiled novel findings from a comprehensive genomic analysis of 6,235 patients across 15 hematologic malignancies at AACR (Free AACR Whitepaper). The results include the first-ever observance of recurrent RNA splicing factor mutations in non-Hodgkin’s lymphoma and multiple myeloma, the company said. In its announcement, H3 said the findings demonstrate the "continued emergence of splicing factor mutations as a hallmark of dozens of hematologic and solid tumor cancers, their potential role in tumor formation and growth, and, thus, the opportunity to advance a new class of therapies."
Checkmate Pharmaceuticals – Data from an ongoing Phase Ib trial shows that Checkmate’s Toll-like receptor 9 CMP-001 combined with Merck’s Keytruda demonstrated "deep and durable clinical responses" in patients with advanced melanoma who are resistant to prior anti-PD-1 checkpoint inhibition. Data shows that the combination therapy brought about the systemic regression of "non-injected cutaneous, nodal, hepatic, and splenic metastases in patients who had progressed on a median of two prior therapies."

Deciphera Pharmaceuticals – Cambridge, Mass.-based Deciphera unveiled preclinical data that showed DCC-2618, a KIT and PDGFRα kinase switch control inhibitor, inhibited primary and secondary KIT mutations and primary PDGFRα mutations in gastrointestinal stromal tumors (GIST) and systemic mastocytosis. Deciphera said in comparison to other approved compounds, DCC-2618 demonstrated the "broadest profile of inhibition" in the preclinical study.
NewLink Genetics – In a poster presentation at AACR (Free AACR Whitepaper) NewLink showed that indoximod has a unique method of action in modulating AhR-driven transcription of genes. The company said the different mechanism of action may contribute to antitumor immune responses in the IDO pathway, as well as independent of that IDO pathway. The company said indoximod regulates the "differentiation of helper T cells toward an immuno-stimulatory helper function and downregulates genes that control the differentiation of T cells into immuno-suppressive regulatory T cells in an AhR dependent manner."

Torque – Preclinical data presented by Torque at AACR (Free AACR Whitepaper) shows the company’s Deep-Primed IL-15 and Deep-Primed IL-12 cellular therapy programs demonstrated superior activity compared to systemically administered IL-15 and IL-12. Torque’s Deep-Primed therapeutics use material engineering to anchor immune-stimulatory drugs directly to the surface of multi-targeted, antigen-primed T cells. This allows the activation of the adaptive and innate immune system with pharmacologic control in the tumor microenvironment, according to the company.
Laboratory for Advanced Medicine – With a push to advance early cancer diagnostics California-based Laboratory for Advanced Medicine revealed data that demonstrates the utility of circulating tumor DNA (ctDNA) methylation markers in the diagnosis, surveillance and prognosis of Hepatocellular Carcinoma. In an AACR (Free AACR Whitepaper) presentation, the company said the findings support that "ctDNA carrying cancer-specific genetic and epigenetic aberrations may enable a non-invasive liquid biopsy for the diagnosis and monitoring of cancer."
PharmaMar – New data presented by PharmaMar at AACR (Free AACR Whitepaper) showed that plitidepsin interacts with and inhibits PKR on the eEF1A2 enzyme. Plitidepsin inhibits this interaction obtaining the induction of cell death, the company announced. PharmaMar said through the bonding to eEF1A2, plitidepsin annuls the oncogenic properties of its target.