On March 14, 2018 Leap Therapeutics, Inc. (NASDAQ:LPTX), a biotechnology company developing targeted and immuno-oncology therapeutics, reported its presented promising clinical data from the study evaluating DKN-01, Leap’s anti-DKK1 monoclonal antibody, as a monotherapy in patients with advanced esophagogastric cancer (Press release, Leap Therapeutics, MAR 19, 2018, View Source [SID1234524889]). In addition, Leap announced that the first patient has been enrolled in the study evaluating DKN-01 in patients with gynecological cancers. Leap also announced two upcoming scientific presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2018 Annual Meeting.

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DKN-01 Monotherapy in Patients with Esophagogastric Cancer
Data presented today at the Barclays Global Healthcare Conference included 16 patients with advanced esophagogastric cancer who were treated with DKN-01 monotherapy. Central imaging review identified two patients (12.5%) with a best response of a partial response and five patients (31.3%) with stable disease, representing a total disease control rate of 43.8%. This cohort of patients had received many different lines of prior therapy. One patient who had failed prior investigational immunotherapies, including a PD-L1 antagonist and IDO inhibitor, had a partial response on DKN-01 monotherapy and remained on study for over a year.

"The results of the DKN-01 monotherapy cohort demonstrate promising single agent activity in a very difficult to treat population of heterogeneous esophagogastric cancer. This data, in addition to the encouraging activity we have seen with DKN-01 in preclinical models and in patients in combination with chemotherapy, provides a strong foundation for our ongoing study in combination with the anti-PD-1 therapy Keytruda," commented Cynthia Sirard, MD, Vice President of Clinical Development for Leap.

DKN-01 Gynecologic Malignancies Study

Leap also announced that the first patient has been dosed in a Phase 2 clinical trial evaluating DKN-01 as a monotherapy and in combination with paclitaxel chemotherapy in patients with advanced endometrioid gynecologic malignancies. The study is part of Leap’s strategy to treat cancer patients with documented mutations of the Wnt signaling pathway, a biomarker identified in patients who have responded to DKN-01 therapy. Data presented today by Leap demonstrates that uterine cancer patients with these mutations often have elevated intratumoral levels of DKK1.

"Mutations of the Wnt pathway, particularly beta-catenin, are highly prevalent in endometrioid gynecologic cancers, and often thought to be a driver of an aggressive subgroup of the disease," commented Michael Birrer, M.D., Ph.D., Director of the Comprehensive Cancer Center at the University of Alabama at Birmingham and an investigator on the study. "We are excited to begin this trial of DKN-01, which has shown promising activity in patients with Wnt signaling mutations in other solid tumor malignancies."

The study is a Phase 2 basket study evaluating DKN-01 as a monotherapy and in combination with paclitaxel in patients with relapsed/refractory endometrioid endometrial cancer (EEC) or endometrioid ovarian cancer (EOC). The study contains four groups and is designed to evaluate the efficacy, safety, and pharmacodynamics of DKN-01 monotherapy and combination therapy in both EEC and EOC, with each group following a 2-stage Simon Minimax design. The study will enroll approximately 94 patients, of which ~ 50% will be required to have documented activating mutations of beta-catenin or other Wnt signaling alterations.

Upcoming Presentation at AACR (Free AACR Whitepaper) Annual Meeting
Additionally, Leap announced two poster session presentations at the AACR (Free AACR Whitepaper) Annual Meeting, being held April 14 – 18, 2018, in Chicago, IL.

Abstract Number and Title: 1710 / 5 – DKN-01, a therapeutic DKK1 neutralizing antibody, has immune modulatory activity in nonclinical tumor models

Session Title: Immune Response to Therapies 2

Session Date and Time: April 16, 2018, 8:00 AM – 12:00 PM

Session Location: McCormick Place, Poster Section 32

Abstract Number and Title: 1699 / 24 – Treatment with agonist anti-GITR antibody after chemotherapy enhances tumor immunity

Session Title: Immune Checkpoints 1

Session Date and Time: April 16, 2018, 8:00 AM – 12:00 PM

Session Location: McCormick Place, Poster Section 31

On March 19, 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 that the U.S. Food and Drug Administration (FDA) Office of Orphan Products Development has granted Orphan Drug Designation to CLR 131, the company’s lead Phospholipid Drug Conjugate (PDC) product candidate, for the treatment of neuroblastoma, a rare pediatric cancer (Press release, Cellectar Biosciences, MAR 19, 2018, View Source [SID1234524884]).

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"Neuroblastoma is the third most common childhood cancer for which there are currently no approved treatments for children with relapsed or refractory disease," stated John Friend, M.D., chief medical officer of Cellectar. "The FDA’s granting of orphan drug designation for CLR 131 highlights the significant need for new treatments for children with neuroblastoma, and we believe that the targeted delivery of CLR 131 represents a promising novel approach to its treatment."

Orphan drug designation provides seven year market exclusivity benefit, increased engagement and assistance from the FDA, tax credits for certain research, research grants and a waiver of the New Drug Application user fee. Neuroblastoma is recognized by the FDA as an orphan disease, usually defined as a condition that affects fewer than 200,000 people nationwide.

The FDA previously accepted the Company’s Investigational New Drug application for a Phase 1 open-label, dose-escalating study to evaluate the safety and tolerability of a single intravenous administration of CLR 131 in up to 30 children and adolescents with cancers including neuroblastoma, sarcomas, lymphomas (including Hodgkin’s lymphoma) and malignant brain tumors. Cellectar expects to initiate this study during the second quarter of 2018.

On March 19, 2018 H3 Biomedicine Inc., a clinical stage biopharmaceutical company specializing in the discovery and development of next generation cancer medicines using its data science and precision chemistry product engine, reported that management will present an overview of the company at the BioCentury 25th Annual Future Leaders in the Biotech Industry Conference on Friday, March 23, 2018, at 10:15 a.m. EST at the Millennium Broadway Hotel & Conference Center in New York (Press release, H3 Biomedicine, MAR 19, 2018, View Source [SID1234524968]).

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On March 19, 2018 RedHill Biopharma Ltd. (NASDAQ:RDHL) (Tel-Aviv Stock Exchange:RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company primarily focused on late clinical-stage development and commercialization of proprietary drugs for gastrointestinal diseases and cancer, reported the presentation of a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2018 Annual Meeting (Press release, RedHill Biopharma, MAR 19, 2018, View Source [SID1234524878]). The abstract (number 4200) will be presented by Mark L. Levitt, MD, Ph.D., Medical Director, Oncology at RedHill, on Tuesday, April 17, 2018 from 1:00 PM to 5:00 PM CDT, at McCormick Place, Chicago, IL.

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The abstract1 presentation, entitled ‘New potential therapeutic applications of WX-UK1, as a specific and potent inhibitor of human trypsin-like proteases’, describes data from non-clinical studies concluding that WX-UK1, the active metabolite of RHB-107 (formerly MESUPRON) (INN: upamostat), is a potent and specific inhibitor of five human serine proteases (trypsin-3, trypsin-2, trypsin-1, matriptase-1 and trypsin-6). Several of these serine proteases are associated with cancer progression and metastasis. The non-clinical studies suggest new potential therapeutic applications of WX-UK1 in oncology and inflammatory gastrointestinal diseases. The abstract was authored by scientists from the Department of Molecular Biology and Genetics of Aarhus University in collaboration with RedHill2.

RHB-107 is a proprietary, first-in-class, orally-administered potent serine protease inhibitor, presenting a new non-cytotoxic approach to cancer therapy, as well as other indications of high unmet need, such as inflammatory digestive diseases and inflammatory lung diseases. RHB-107 has undergone several Phase I studies and two Phase II proof-of-concept studies in cancer patients.

With the recent identification of several serine proteases as high-affinity molecular targets, RedHill is evaluating utilization of RHB-107 in both cancer and inflammatory digestive diseases.

About RHB-107 (upamostat):
RHB-107 (formerly MESUPRON) (INN: upamostat) is a proprietary, first-in-class, orally-administered potent inhibitor of several serine proteases targeting cancer and inflammatory gastrointestinal diseases. Protease inhibitors have been shown to play key roles in tumor invasion and the metastasis process. High levels of certain proteases are associated with poor prognosis in various solid tumor cancers, such as pancreatic, gastric, breast and prostate cancers. RHB-107 was previously granted FDA Orphan Drug designation for the treatment of pancreatic cancer. RHB-107 presents a new non-cytotoxic approach to cancer therapy with several potential mechanisms of action to inhibit tumor invasion and metastasis. RHB-107 has undergone several Phase I studies and two Phase II proof-of-concept studies. The first Phase II study was in locally-advanced, non-metastatic pancreatic cancer and the second study in metastatic breast cancer in combination with first-line chemotherapeutic agents. RedHill was granted a new patent from the United States Patent and Trademark Office (USPTO) directed to a combination of RHB-107, YELIVA, RedHill’s two Phase II-stage investigational compounds, and a known antibiotic. RedHill acquired the exclusive worldwide rights to RHB-107, excluding China, Hong Kong, Taiwan and Macao, from Germany’s Heidelberg Pharmaceuticals (formerly WILEX AG) for all indications.

On March 19, 2018 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported dosing of the first patient in a Phase 1 study of AG-270, a first-in-class methionine adenosyltransferase 2a (MAT2A) inhibitor (Press release, Agios Pharmaceuticals, MAR 19, 2018, View Source [SID1234524881]). This open-label, dose-escalation and expansion study investigates AG-270 in patients with solid tumors or lymphoma with deletion of the metabolic gene methylthioadenosine phosphorylase (MTAP).

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"In addition to significant milestones for our late-stage portfolio this year, we are pleased to demonstrate the continued productivity of our research engine by advancing our sixth internally discovered molecule into the clinic," said Scott Biller, M.D., chief scientific officer of Agios. "As a first-in-class MAT2A inhibitor, AG-270 has the potential to benefit the large number of patients whose cancer is characterized by the loss of MTAP. We look forward to conducting the early clinical work that will explore the pharmacology and clinical activity of MAT2A inhibition in tumors carrying this deletion."

"We are excited to participate in the development of this novel and targeted approach to cancer treatment," said Howard (Skip) Burris, M.D., chief medical officer and president of clinical operations at Sarah Cannon. "Bringing AG-270 into the clinic represents an opportunity for Sarah Cannon and Agios to continue a partnership that began with the IDH inhibitors and remains focused on transforming cancer care and personalizing treatment."

AG-270 Phase 1 Study Design

The purpose of this Phase 1 multi-center, open-label study is to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-270 in approximately 50 patients with advanced solid tumors or lymphoma with MTAP deletion. AG-270 will be administered as a single agent dosed orally once daily in 28-day cycles. The first part of the study is a dose-escalation phase in which cohorts of patients will receive ascending doses of AG-270 to determine the maximum tolerated dose (MTD) or optimal dose. The second part of the study is a dose expansion phase where additional patients will receive AG-270 at the MTD or optimal dose to further evaluate its safety, tolerability and clinical activity as a potential dose for future studies. Patients must have evidence of loss of the MTAP protein from their tumor tissue, or evidence of loss of the CDKN2A tumor suppressor gene (commonly co-deleted with the MTAP gene), in order to be eligible for the study. Please refer to www.clinicaltrials.gov for additional clinical trial information.

About the MAT2A Inhibitor AG-270
AG-270 is part of a 2016 global research collaboration agreement with Celgene Corporation. Through Phase 1 dose escalation, Celgene has the option, for a fee of at least $30 million, to participate in a worldwide cost and profit share with Agios. Upon exercise of the option the parties will share all development costs, subject to specified exceptions, and any profits on net sales and Agios will be eligible for up to $169 million in clinical and regulatory milestone payments for the program. As described in a 2016 Cell Reports publication, Agios discovered that MAT2A is a component of a novel pathway in MTAP-deleted tumors which, when inhibited, results in robust anti-tumor activity. Preclinical data presented at the 2017 Keystone Tumor Metabolism meeting demonstrated that small molecule inhibitors of MAT2A are efficacious in MTAP-deleted tumor xenograft models.