On December 18, 2018 Delcath Systems, Inc. (OTCQB: DCTH), an interventional oncology company focused on the treatment of primary and metastatic cancers of the liver, reported that the independent Data Safety Monitoring Board (DSMB) of the Registration trial for Patients with Hepatic Dominant Ocular Melanoma (The FOCUS Trial) completed another pre-specified review of safety data for treated patients in the trial (Press release, Delcath Systems, DEC 18, 2018, View Source;p=RssLanding&cat=news&id=2381000 [SID1234532112]). This review was conducted on data collected from both the prior randomized protocol and the amended single-arm protocol for the FOCUS Trial. The DSMB again recommended continuation of the study without modification.

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In July, the Company announced that it has amended the protocol for the FOCUS trial, which is now enrolling as a single-arm, multi-center open label study. Safety data collected have not been modified as a result of the amendment, and safety data from both the randomized and single-arm protocols will be pooled in any analyses submitted to the Food & Drug Administration as part of a New Drug Application.

The FOCUS trial, now entitled A Single-arm, Multi-Center, Open-Label Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Melphalan/HDS Treatment in Patients with Hepatic-Dominant Ocular Melanoma (The FOCUS Trial), is enrolling a minimum of 80 patients with ocular melanoma metastatic to the liver. Patients previously enrolled under the prior randomized protocol continue to be treated and evaluated as part of the amended trial, and periodic DSMB reviews will continue to be conducted.

Commenting on the announcement, Jennifer K. Simpson, Ph.D., MSN, CRNP President and CEO of Delcath, said, "We are pleased with the safety profile observed by our therapy in the trial thus far, and the trial remains on track to complete enrollment by June 2019."

On December 17, 2018 AOP Orphan Pharmaceuticals AG (AOP Orphan) reported that EMA´s CHMP adopted a positive opinion for approval of Ropeginterferon alfa-2b/BESREMi indicated as monotherapy in adults for the treatment of Polycythaemia vera without symptomatic splenomegaly (Press release, AOP Orphan Pharmaceuticals, DEC 17, 2018, View Source [SID1234533574]).

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Ropeginterferon alfa-2b/BESREMi is a novel, long-acting interferon, which is administered once every two weeks, or monthly after stabilization of hematological parameters. This treatment schedule is expected to lead to overall better safety, tolerability and adherence compared to conventional pegylated interferons.

AOP Orphan has been running the BESREMi clinical development in PV since 2010. The latest phase III data, three years treatment, and phase II data, up to seven years treatment, were presented at ASH (Free ASH Whitepaper) 2018. In summary, BESREMi showed high hematologic and clinical response rates with good tolerability.


In addition, BESREMi showed high molecular response rates, associated with the ability to reduce allelic burden of both mutant JAK2 and importantly also non-JAK2 mutations, which are believed to have a role in disease progression.

Andreas Steiner, Chief Executive Officer of AOP Orphan commented: "Although interferons are a treatment modality widely used throughout the myeloproliferative neoplasms including CML, BESREMi will be the first licensed interferon in any of these indications. Physicians experienced in the management of the disease and administration of BESREMi during the clinical studies expect many advantages for the patients with PV."

About Ropeginterferon alfa-2b/BESREMi
Ropeginterferon alfa-2b/BESREMi is a novel, long-acting, mono-pegylated proline interferon (ATC L03AB15) with improved pharmacokinetic properties offering improved tolerability and adherence to treatment. It is administered once every two weeks, or monthly during long-term maintenance, and is expected to be the first interferon approved for PV worldwide.

Ropeginterferon alfa-2b was discovered by PharmaEssentia, a long-term partner of AOP Orphan. In 2009, AOP Orphan has in-licensed from PharmaEssentia Corporation the exclusive rights for clinical development and commercialization of Ropeginterferon alfa-2b in PV, other MPNs and CML for European, Commonwealth of Independent States (CIS), and Middle Eastern markets.

About Polycythemia Vera
Polycythemia Vera (PV) is a cancer of the blood-building cells in the bone marrow resulting in a chronic increase of red blood cells, white blood cells and platelets. This condition may result in circulatory disorders such as thrombosis and embolism, as well as malignant transformation to myelofibrosis or leukemia. While the molecular mechanism underlying PV is still subject of intense research, current results point to a set of acquired mutations, the most important being a mutant form of JAK2 that make the malignant clone.

On December 17, 2018 C4X Discovery Holdings plc (AIM: C4XD), a pioneering drug discovery company, reported that it has entered into an exclusive target discovery partnership with Horizon Discovery Group plc ("Horizon", AIM: HZD), a global leader in the application of gene editing and gene modulation technologies (Press release, C4X Discovery, DEC 17, 2018, View Source [SID1234533248]). The partnership aims to validate novel synthetic lethal oncology targets that have been identified by Horizon’s cutting-edge CRISPR-Cas9 technology leading to the generation of potential new drugs for patients with limited effective treatments such as colorectal and lung cancer.

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C4XD aims to apply its proprietary 4D shape-based chemistry technology (Conformetrix) to discover drug candidates directed against these high value, novel, synthetic lethality targets and out-license them to clinical development partners. This discovery partnership bolsters C4XD’s oncology pipeline, a high priority therapeutic area for the company.

The therapeutic concept of harnessing synthetic lethality in cancer with tumour-specific mutations has been demonstrated with the recent approval of the poly(ADP-ribose) polymerase (PARP) inhibitors Lynparza Zejula and Rubraca. These drugs are effective in indications that are poorly served by immunotherapy drugs, such as checkpoint inhibitors, and have become an established treatment in ovarian cancer. They work by targeting a specific DNA repair pathway that cancer cells, with mutations such as BRCA, become over-reliant on. Inhibiting this critical DNA repair pathway causes the tumour cells to self-destruct, resulting in the terminology ‘synthetic lethality’. The pharmaceutical industry is now rushing to fill its clinical pipelines with investigational drugs, identified by empirical research, that might produce similar efficacy in cancers where PARP inhibitors are not effective.

However, recent advancements in the gene-editing tool, CRISPR-Cas9, has enabled systematic ‘functional genomic’ screening to identify novel synthetic lethal genes in cancer cells with specific mutations. Horizon has utilised its target discovery platform to conduct high quality CRISPR gene knock-out studies across multiple cancer cell lines, screening around ~3000 genes suitable as the basis for small molecule drug targets. This cutting-edge approach has identified a shortlist of ~20 novel, high value synthetic lethal genes following a secondary screen to further validate them as targets. The partnership has been established to complete the target validation package for these novel targets, leading to the initiation of drug discovery programmes by C4XD should it exercise its options on a target-by-target basis. C4XD will provide the funding for the work plan and Horizon will receive a share of all future revenues C4XD receives should any drug discovery programmes emerging from the partnership be out-licensed for clinical development.

Dr Craig Fox, Chief Scientific Officer of C4XD, said: "PARP inhibitors are transforming the treatment of ovarian cancer, particularly in patients with BRCA mutations and so identifying the next generation of synthetic lethality drug targets is a key priority to develop new therapies for cancers patients who are not responsive to current treatments. This partnership with Horizon gives C4XD access to a comprehensive proprietary CRISPR screening dataset that has selected the most promising novel drug targets in colon and lung cancer. We look forward to working with the highly experienced team at Horizon to complete the target validation package for these novel genes and initiate drug discovery programmes to generate high value pre-clinical licensable assets for partnering."

Dr Jon Moore, Horizon’s Chief Scientific Officer added: "Drugging the cancer genome now requires new synthetic lethal therapies that can exploit the vulnerabilities in patient’s tumours that are created by mutations in undruggable cancer driver genes. Horizon’s internal research program has used powerful CRISPR technology to open a new window into how cancer cells are wired and has identified a cohort of novel targets. We are delighted to have secured this collaboration with C4X Discovery, which applies a powerful drug discovery engine to the first-in-class opportunities for transformational medicines represented by the targets Horizon has found and allows Horizon to share in the upside."

On December 17, 2018 TG Therapeutics, Inc. (NASDAQ: TGTX) and Dana-Farber Cancer Institute reported the publication of results from the multicenter Phase 1/1b trial of umbralisib (TGR-1202), TG Therapeutics’ novel once-daily PI3K delta inhibitor, in combination with ibrutinib, the oral Bruton’s tyrosine kinase (BTK) inhibitor, in Lancet Haematology (Press release, TG Therapeutics, DEC 17, 2018, View Source [SID1234532247]). This investigator-initiated trial was conducted at Dana-Farber Cancer Institute and four additional academic and community sites across the USA in collaboration with the Leukemia and Lymphoma Society Blood Cancer Research Partnership with funding by TG Therapeutics. The publication includes safety and efficacy information from a total of 42 relapsed or refractory patients, 21 with chronic lymphocytic leukemia (CLL) and 21 with mantle cell lymphoma (MCL).

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In this study, the combination of umbralisib and ibrutinib was well tolerated and consistent with the additive toxicity profile of the two drugs individually. No dose-limiting toxicities were observed, and the maximum-tolerated dose of umbralisib when combined with ibrutinib was not reached. The recommended phase 2 dose of umbralisib when given in combination with ibrutinib was 800 mg once daily. Importantly, serious immune-mediated toxicities were not observed with this combination, as had previously been reported with combinations of different agents targeting this pathway, with only one case of transient Grade 3 transaminitis and no Grade 3/4 colitis or pneumonitis. The combination of umbralisib and ibrutinib was also clinically active, with 90% of relapsed/refractory CLL patients achieving an overall response (n=19), of which 62% (n=13) achieved a partial response or partial response with lymphocytosis, and 29% (n=6) achieved a complete response. Of the 21 patients treated with MCL, 67% (n=14) achieved an overall response, of which 48% (n=10) achieved a partial response and 19% (n=4) achieved a complete response.

These data are described further in the manuscript entitled, "Umbralisib in combination with ibrutinib in patients with relapsed or refractory chronic lymphocytic leukaemia or mantle cell lymphoma: a multicenter phase 1–1b study," which was published today in Lancet Haematology. The online version of the article can be accessed at http://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(18)30196-0/fulltext.

"Our study demonstrates for the first time that it is feasible to combine two agents targeting B cell receptor pathway kinases in patients with B cell malignancies," said Matthew Davids, MD, MMSc, Associate Director of the Center for Chronic Lymphocytic Leukemia at Dana-Farber. Dr. Davids continued, "We are particularly encouraged by the depth of response in the CLL patients, which compares favorably to historical data for ibrutinib monotherapy in this relapsed population. Our data support further exploration of dual BCR pathway blockade in CLL and other B cell malignancies."

Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer, stated "We want to thank Dr. Davids and the team at Dana-Farber, and most importantly the patients who participated in this trial. We are excited to publish the first ever data evaluating the all oral combination of a PI3K delta inhibitor with a BTK inhibitor and believe this paper further highlights the favorable safety profile and combinability of umbralisib as compared to prior generation PI3k deltas. We believe these data support our plans to develop combinations utilizing umbralisib plus our BTK inhibitor, TG-1701, which has already demonstrated activity in patients in early clinical studies."

On December 17, 2018 Daiichi Sankyo Company, Limited ("Daiichi Sankyo") and AnHeart Therapeutics Inc. ("AnHeart Therapeutics") reported they have entered into a worldwide exclusive license agreement ("Agreement") for DS-6051, Daiichi Sankyo’s selective ROS1/NTRK inhibitor, currently in phase 1 development in the United States and Japan (Press release, Daiichi Sankyo, DEC 17, 2018, View Source [SID1234532114]).

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Under the terms of the agreement, Daiichi Sankyo grants AnHeart Therapeutics worldwide exclusive rights for the development, manufacturing and commercialization of DS-6051. While Daiichi Sankyo and AnHeart Therapeutics will collaborate to continue two ongoing phase 1 studies, AnHeart Therapeutics will be responsible for further development of DS-6051 worldwide. Daiichi Sankyo will receive an upfront payment and is eligible for clinical, regulatory and sales milestone payments, as well as royalties on worldwide net sales of DS-6051. Financial terms of the agreement are not disclosed.

"We continue to look for innovative ways to maximize the potential of promising compounds in our oncology pipeline in order to deliver on our mission of transforming science into value for patients with cancer," said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. "We are confident that AnHeart Theraeputics will use the resources necessary to deliver a fast-to-market strategy to potentially bring this novel ROS1/NTRK inhibitor to patients as quickly as possible."

"We thank Daiichi Sankyo for its trust in AnHeart Therapeutics and its continued support in further developing the DS-6051 asset worldwide. DS-6051 is currently being studied in two phase 1studies for cancers bearing ROS1 or NTRK fusion mutations, and is a leading asset in our pipeline," commented Junyuan Wang, PhD, Chief Executive Officer, AnHeart Therapeutics. "It is our priority to move DS-6051 through the global regulatory pathways with a fast-to-market approach. We will communicate with regulatory agencies to initiate multiple global phase 2 trials of DS-6051 immediately after the transfer of clinical development responsibilities is completed."

About DS-6051

DS-6051 is an oral, selective small molecule ROS1/NTRK inhibitor currently being evaluated in two phase 1 clinical studies in patients with solid tumors harboring either a ROS1 or NTRK fusion gene and neuroendocrine tumors in the U.S. and Japan. Preliminary safety and efficacy data of DS-6051 from the first part of the U.S.-based phase 1/1b study were presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.1