On April 16, 2018 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS) reported the presentation of preclinical data demonstrating the robust cell killing ability of CG’806, a pan-FLT3/pan-BTK inhibitor, in multiple types of AML and B-cell malignancies (Press release, Aptose Biosciences, APR 16, 2018, View Source;p=RssLanding&cat=news&id=2342648 [SID1234525329]). Data further demonstrated that CG’806 targets multiple pathways and overcomes drug resistance seen with other inhibitors. The data were presented in a poster on Sunday, April 15, 2018 at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Conference being held April 14-18, in Chicago, IL.

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The poster, entitled CG’806, a first-in-class pan-FLT3/pan-BTK inhibitor, targets multiple pathways to kill diverse subtypes of acute myeloid leukemia and B-cell malignancy in vitro, explores the potency and molecular mechanisms of the pan-FLT3/pan-BTK inhibitor CG’806 in hematologic malignancies relative to other FLT3 or BTK inhibitors commercialized or in development. The Aptose research team led by Dr. Hannah Zhang, Senior Director of Research, demonstrated that in FLT3-ITD AML cells, CG’806 induced apoptosis through inhibition of FLT3 signaling, and CG806 was approximately 10-fold more potent than quizartinib. Although FLT3-ITD is found in approximately 30% of AML patient, most AML patients express wild type (WT) FLT3. CG’806 was superior to quizartinib, gilteritinib and crenolanib FLT3 inhibitors in FLT3-WT AML cell lines. In B cell malignancies, BTK signaling plays a pivotal pathogenic role. CG’806 decreased BTK phosphorylation in all malignant B cell lines tested and inhibited cell proliferation and colony formation 50-6,000 times more potently than ibrutinib, an effect explained by the ability of CG’806 to target multiple rescue pathways rather than merely the exclusive inhibition of BTK signaling.

CG’806 demonstrated the ability to target all wild type (WT) and mutant forms of FLT3 and BTK and to inhibit multiple signaling pathways, producing killing of diverse subtypes of hematologic malignancies driven by different genomic aberrations.

"This study directly compares CG’806 to other FLT3 or BTK inhibitors in development and confirms the potent and extended activity we have seen with the molecule," said William G. Rice, Ph.D., Chairman and Chief Executive Officer of Aptose. "As a pan-FLT3/pan-BTK multi-kinase inhibitor that can eliminate tumors in the absence of toxicity in animal models, CG’806 has demonstrated the ability to kill a broad range of AML and B-cell malignancies through inhibition of multiple oncogenic pathways. We are eager to pursue its clinical development."
Separately, Aptose and Oregon Health & Science University (OHSU) Knight Cancer Center researchers also announced new data on CG’806 presented at AACR (Free AACR Whitepaper) (see press release here). Both poster presentations will be published in the AACR (Free AACR Whitepaper) Conference Proceedings. The posters can also be accessed here or at the Publications & Presentations section of the Aptose website, www.aptose.com.

About CG’806
CG‘806 is an oral, first-in-class pan-FLT3/pan-BTK multi-kinase inhibitor. This small molecule demonstrates potent inhibition of wild type and mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), eliminates acute myeloid leukemia (AML) tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with AML. Likewise, CG’806 demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser mutant forms of the BTK enzyme, as well as other oncogenic kinase pathways operative in B cell malignancies, suggesting CG’806 may be developed for various B cell malignancy patients (including CLL, MCL, DLBCL and others) that are resistant/refractory/intolerant to covalent BTK inhibitors. CG’806 is currently in preclinical development in partnership with CrystalGenomics.

On April 16, 2018 Idera Pharmaceuticals, Inc. ("Idera") (NASDAQ:IDRA), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel oligonucleotide therapeutics for oncology and rare diseases, reported it has entered into a clinical development support agreement with Pillar Partners Foundation ("Pillar Partners") (Press release, Idera Pharmaceuticals, APR 16, 2018, View Source [SID1234525345]). Under the terms of the agreement Pillar Partners will provide direct funding to support three investigator initiated clinical trials to further strategically expand the clinical research of IMO-2125, Idera’s toll-like receptor ("TLR") 9 agonist into broader melanoma populations and other solid tumors. For these trials, Idera will provide IMO-2125. Idera is currently enrolling a Phase 3 ("ILLUMINATE-301") trial of intratumoral administration of IMO-2125 in combination with ipilimumab in patients with anti-PD-1 refractory metastatic melanoma.

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The three trials within the terms of this agreement are:
A Phase 1/2 open label study of intratumoral IMO-2125 in combination with intratumoral ipilimumab and IV nivolumab in a protocol open to multiple tumor types including non-small cell lung cancer ("NSCLC"), melanoma, squamous cell carcinoma of the head and neck and urothelial carcinoma. The principal investigator initiating this trial is Aurélien Marabelle, MD, PhD, Clinical Director of the Cancer Immunotherapy Program at Institut Gustave Roussy, Villejuif, France.

A Phase 2 study of intratumoral IMO-2125 in combination with IV pembrolizumab in patients with NSCLC. The principal investigator initiating this trial is Arafat Tfayli, MD, FRCP, Professor of Clinical Medicine, Director of Research, NK Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon.

A Phase 2 placebo controlled study of intradermal administration of IMO-2125 in patients with T3/T4 primary melanoma scheduled to undergo a combined re-excision and sentinel node biopsy procedure. The principal investigators initiating this trial are Bas Koster, MD, Fons van den Eertwegh MD, PhD, and Tanja de Gruijl, PhD, who is Professor of Translational Tumor Immunology and Co-Director of the Cancer Immunology Program at the VU University Medical Center, Cancer Center Amsterdam, The Netherlands.
"We are eager to expand our knowledge and understanding of the various cancer types and combinations in which IMO-2125 can play a significant role in improving outcomes beyond our current registrational focus with our ILLUMINATE 301 program," stated Joanna Horobin, M.B., Ch. B., Idera’s Chief Medical Officer. "We look forward to working with these investigators to provide the support they need to initiate these trials before the end of the year," said Shah Rahimian, MD, Idera’s Oncology Medical Lead. "
"We have long believed and understood that the mechanism for IMO-2125 has broad potential and plays a central role in IO combinations beyond PD-1 refractory melanoma and through this financial grant, we are able to help light the spark to further expand our ability to test this hypothesis in multiple tumor types with expert clinical investigators," stated Youssef El Zein, Managing Partner, Pillar Invest Corporation.

On April 16, 2018 Apexian Pharmaceuticals, a leading clinical-stage biotechnology company focused on developing safe and effective therapy for patients with high unmet medical needs, reported that it will present two key poster sessions at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Meeting which will be held at McCormick Place in Chicago, Illinois from April 14 – 18, 2018 (Press release, Apexian Pharmaceuticals, APR 16, 2018, View Source [SID1234525416]). Dr. Mark Kelley, Apexian’s Chief Scientific Officer, along with the research team will available at the posters session. The company will present two posters on combination therapy of APX3330 in pancreatic cancer and APE1 signaling pathway.

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"Combination Therapy in PDAC Involving Blockade of the APE1/Ref-1 Signaling Pathway: An Investigation into Drug Synthetic Lethality and Anti-Neuropathy Therapeutic Approach"

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The titles and locations for these sessions are:

"Combination Therapy in PDAC Involving Blockade of the APE1/Ref-1 Signaling Pathway: An Investigation into Drug Synthetic Lethality and Anti-Neuropathy Therapeutic Approach"

Session Date and Time: Tuesday, April 17, 2018 from 1:00 – 5:00 PM
Location: McCormick Place South, Exhibit Hall A, Poster Section 37

"APE1/Ref-1 Redox Signaling Regulates HIF1a-mediated CA9 Expression in Hypoxic Pancreatic Cancer Cells: Combination Treatment in Patient-derived Pancreatic Tumor Models"

Session Date and Time: Monday, April 16, 2018 from 1:00 – 5:00 PM
Location: McCormick Place South, Exhibit Hall A, Poster Section 41

The poster sessions will add significant new information gathered on the effectiveness of Apexian’s lead clinical candidate, APX3330, and the ongoing research on the APE1/Ref-1 target.

On April 16, 2018 Bexion Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company focused on rare brain tumors, reported that the four abstracts submitted for presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting held June 1-5, 2018 in Chicago, Illinois have all been accepted (Press release, Bexion, APR 16, 2018, View Source [SID1234525565]).

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One of the accepted presentations is entitled "First-in-human, First-in-class Phase 1a Study of BXQ-350 for Solid Tumors and Gliomas".

The ASCO (Free ASCO Whitepaper) Annual Meeting brings together more than 32,000 oncology professionals from around the world to discuss state-of-the-art treatment modalities, new therapies, and ongoing controversies in the field.

About BXQ-350

BXQ-350 is a unique formulation of a synthetically produced, human lysosomal protein, Saposin C (sphingolipid activator protein, or SapC), and the phospholipid dioleoylphosphatidylserine (DOPS).

On April 16, 2018 BeiGene, Ltd. (NASDAQ:BGNE), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly targeted and immuno-oncology drugs for the treatment of cancer, reported that the first patient was dosed in a global Phase 2 clinical trial of tislelizumab, an investigational anti-PD-1 antibody, in patients with relapsed or refractory mature T- and natural killer (NK)-cell lymphomas (Press release, BeiGene, APR 16, 2018, View Source;p=RssLanding&cat=news&id=2342635 [SID1234525330]). Tislelizumab is also being studied in global Phase 3 trials in solid tumors, including non-small cell lung cancer, hepatocellular carcinoma, and esophageal squamous cell carcinoma, and two pivotal Phase 2 trials in China in relapsed/refractory classical Hodgkin lymphoma and urothelial cancer.

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"We are pleased to be enrolling patients in our first global Phase 2 study in hematology of tislelizumab, for which we maintain global development and commercial rights," commented John V. Oyler, Founder, Chief Executive Officer, and Chairman of BeiGene.

"We believe that patients with relapsed or refractory mature T-cell and NK-cell lymphomas represent a significant unmet need. There are no currently approved treatments for the majority of mature T-cell lymphomas, in particular extranodal NK/T-cell lymphomas. We believe that these virally-associated diseases represent logical targets for checkpoint inhibition and we are excited to evaluate tislelizumab as a potential treatment option for these patients," commented Jane Huang, M.D., Chief Medical Officer, Hematology, at BeiGene.

The Phase 2, open-label, multi-center trial is designed to assess the efficacy and safety of tislelizumab in patients with relapsed or refractory mature T- and NK-cell neoplasms. Patients will receive 200 mg of tislelizumab every three weeks in each of the trial’s two histological cohorts:

Cohort 1 – patients with relapsed or refractory extranodal NK/T cell lymphoma (nasal or non-nasal type); and
Cohort 2 – patients with other mature T-cell neoplasms, limited to histologies including peripheral T-cell lymphoma not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma, and anaplastic large cell lymphoma.
Approximately 90 patients who had previously received appropriate first-line systemic therapy and experienced disease progression are planned to be enrolled in Greater China (including Hong Kong and Taiwan), Italy, Germany, France and the United States. The primary efficacy endpoint is objective response rate as determined by independent central review. Secondary endpoints include duration of response, progression-free survival, overall survival, rate of complete response or complete metabolic response, and time to response.
"Tislelizumab has shown promising anti-tumor activity and has been generally well-tolerated in clinical trials to-date in patients with a variety of cancers. We are excited to test the efficacy and safety of this agent in NK/-T cell lymphomas, where new treatment options are badly needed," said Huiqiang Huang, M.D., Chief Physician at the Sun Yat-sen University Cancer Center, Guangdong Province, China, and a member of the steering committee of the trial.
For more information about the trial, patients and physicians should email BeiGene at [email protected].
About Mature T- and NK-cell Neoplasms

T-lymphocytes (T-cells) are a type of white blood cell that can develop into lymphoma, or blood cancer. T-cell lymphomas account for approximately 10-15 percent of all non-Hodgkin’s lymphomas.i Natural killer (NK) cell neoplasms are more rare but are generally grouped with other T-cell lymphomas.ii The World Health Organization classifies several different types of leukemia under the term Mature (peripheral) T-cell Neoplasms (abnormal mass of tissue or blood), including: T-cell prolymphocytic leukemia, T-cell granular lymphocytic leukemia, aggressive NK-cell leukemia, adult T-cell lymphoma/leukemia (HTLV-1 positive), extranodal NK/T-cell lymphoma/ nasal type, enteropathy-type T-cell lymphoma, hepatosplenic gamma-delta T-cell lymphoma, subcutaneous panniculities-like T-cell lymphoma, mycosis fungoides/Sezary syndrome, anaplastic large-cell lymphoma, T-/null cell, primary cutaneous type; peripheral T-cell lymphoma; angioimmunoblastic T-cell lymphoma, anaplastic large-cell lymphoma, T-/null cell, primary systemic type.

About Tislelizumab
Tislelizumab (BGB-A317) is an investigational humanized monoclonal antibody that belongs to a class of immuno-oncology agents known as immune checkpoint inhibitors. It is designed to bind to PD-1, a cell surface receptor that plays an important role in downregulating the immune system by preventing the activation of T-cells. Tislelizumab has demonstrated high affinity and specificity for PD-1. It is potentially differentiated from the currently approved PD-1 antibodies in an engineered Fc region, which is believed to minimize potentially negative interactions with other immune cells, based on preclinical data. Tislelizumab is being developed as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers. BeiGene and Celgene Corporation have a global strategic collaboration for the development of tislelizumab in solid tumor cancers outside of Asia (except Japan).