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 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 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported that initial data from the Phase 1 GARNET trial of TSR-042 (anti-PD-1 antibody) in patients with microsatellite instability high (MSI-H) endometrial cancer and non-small cell lung cancer (NSCLC) presented during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, TESARO, APR 16, 2018, View Source [SID1234525363]).

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"Preliminary results from GARNET presented today at AACR (Free AACR Whitepaper) are the first clinical data from expansion cohorts for TSR-042, our anti-PD-1 antibody," said Mary Lynne Hedley, Ph.D., President and COO of TESARO. "These results demonstrate the clinical activity of TSR-042 and support our unique patient-centric dosing regimen that includes dosing every 6 weeks. We expect to complete enrollment in the MSI-H endometrial cohort of the GARNET trial by the end of the year. A regulatory submission for TSR-042 is planned in 2019. The breadth of TESARO’s immuno-oncology portfolio, which also includes antibodies targeting TIM-3 and LAG-3, enables us to evaluate both monotherapy and novel combination approaches with a goal of providing transformative therapies for people living with cancer."

Preliminary Activity in MSI-H Endometrial Cancer and Non-Small Cell Lung Cancer
GARNET is a multicenter, open-label, Phase 1 dose-escalation study designed to assess the safety, pharmacokinetics, pharmacodynamics, and clinical activity of TSR-042 in patients with advanced solid tumors. Part 1, a weight-based dose escalation study, and part 2A, a fixed-dose safety study, of GARNET have been completed. The ongoing part 2B expansion portion of GARNET is evaluating TSR-042 at a dose of 500 milligrams every 3 weeks for the first 4 cycles, and 1000 milligrams every 6 weeks thereafter in four open cohorts: MSI-H endometrial cancer, MSI-high non-endometrial cancer, MSS endometrial cancer and NSCLC. Data presented at AACR (Free AACR Whitepaper) included efficacy data from the cohorts of patients with MSI-H endometrial cancer and NSCLC from part 2B of the trial.

At the time of data cutoff, 15 patients with MSI-H endometrial cancer and 24 patients with NSCLC had at least 1 tumor assessment. Among the 15 patients with MSI-H endometrial cancer, 7 had partial responses by immune related RECIST (irRECIST) criteria (ORR 47%). Eleven patients continue on therapy, including one patient with a partial response who has thus far received over 42 weeks of TSR-042. Three additional patients (20%) had stable disease.

Among the 24 patients with NSCLC, 7 had partial responses by irRECIST criteria (ORR 29%). Twelve patients continue on therapy, including one patient with a partial response who has thus far received over 36 weeks of TSR-042. Ten additional patients had stable disease (42%), one of whom has continued treatment for over 36 weeks.
Preliminary safety findings among the 120 evaluable patients (including patients with MSI-H endometrial, NSCLC, and other tumor types) indicate TSR-042 is well-tolerated. Grade ≥3 treatment-related treatment-emergent adverse events (TEAEs) were reported in 9 of 120 patients (7%).
Serum concentrations of TSR-042 observed 6 weeks after the 1000 milligram dose were comparable to those observed 3 weeks after the 500 milligram dose, and maximal receptor occupancy was maintained throughout the 6-week dosing interval.

The GARNET study is intended to support a Biologics License Application (BLA) submission to the U.S. Food and Drug Administration (FDA) for patients with MSI-H cancers in 2019.
TESARO Poster Presentations at AACR (Free AACR Whitepaper) (all times local)

Immuno-oncology
Monday, April 16, 2018, 8:00 AM to 12:00 PM
Preliminary safety, efficacy and PK/PD characterization from GARNET, a phase I clinical trial of the anti-PD-1 monoclonal antibody, TSR-042, in patients with recurrent or advanced NSCLC or MSI-H endometrial cancer
Poster Session, Abstract: CT053, Location: Exhibit Hall A, Poster Section 42, Poster Board 6
Monday, April 16, 2018, 8:00 AM to 12:00 PM
Checkpoint inhibitor signatures across endometrial cancer histologies
Poster Session, Abstract: 1687, Location: Exhibit Hall A, Poster Section 31, Poster Board 12
Monday, April 16, 2018, 8:00 AM to 12:00 PM
Simultaneous measurement and significance of PD-1, LAG-3 and TIM-3 expression in human solid tumors
Poster Session, Abstract: 1681, Location: Exhibit Hall A, Poster Section 31, Poster Board 6
Monday, April 16, 2018, 1:00 PM to 5:00 PM
Investigation of the expression profile and functional role of PD-1, TIM-3 and LAG-3 in human tumors
Poster Session, Abstract: 2722, Location: Exhibit Hall A, Poster Section 32, Poster Board 14
Wednesday, April 18, 2018, 8:00 AM to 12:00 PM
Characterization of tumor growth and immune microenvironment in humanized NOG-EXL mice implanted with A549, MDA-MB-436 and A375 cells
Poster Session, Abstract: 5690, Location: Exhibit Hall A, Poster Section 31, Poster Board 26

About GARNET
The ongoing Phase I GARNET trial is evaluating TSR-042 as monotherapy in patients with advanced solid tumors. GARNET included a weight-based dose escalation study (Part 1) and a fixed-dose safety study (Part 2A), both of which have been completed. Results of these studies were used to determine the recommended Phase 2 dose (RP2D; 500 mg Q3W for the first 4 cycles then 1000 mg Q6W). The study is now enrolling patients with MSI-H endometrial cancer, MSI-H non-endometrial cancer, MSS endometrial cancer, and NSCLC into four large expansion cohorts.

About TSR-042
TSR-042 is an investigational humanized anti-programmed death (PD)-1 monoclonal antibody that binds with high affinity to the PD-1 receptor and effectively blocks its interaction with the ligands PD-L1 and PD-L2. TSR-042 is the only anti-PD-1 therapy administered as monotherapy every 3 weeks for 4 doses then every 6 weeks thereafter. TSR-042 was developed as part of the collaboration between TESARO and AnaptysBio, Inc. This collaboration was initiated in March of 2014, and is focused on the development of monospecific antibody drugs targeting PD-1, TIM-3 (TSR-022), and LAG-3 (TSR-033), in addition to a bi-specific antibody drug candidate targeting PD-1/LAG-3 (TSR-075).