On December 13, 2016 Invenra, Inc., a pre-clinical stage bio-pharmaceutical company focused on next-generation therapeutic human antibodies, bispecifics and antibody derivatives, and AgonOx, a biotechnology company developing a pipeline of immunotherapy drugs targeting key regulators of the immune response to cancer, reported a collaboration to identify and characterize a panel of fully human therapeutic monoclonal antibodies (mAbs) against a novel immuno-oncology target that AgonOx has identified utilizing its discovery platform (Press release, Invenra, DEC 13, 2016, View Source [SID1234539840]). Financial details of the deal were not disclosed.

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Invenra’s proprietary platform is based on ultra-high throughput technology allowing function forward screening of full-length antibodies using Invenra’s mAbSeq technology, where antibodies can be directly and quickly interrogated in a multi-plexed fashion with a diverse set of immunotypic and biologically relevant assays. The Invenra technology allows rapid identification of high affinity mAbs with the broadest epitope coverage possible while simultaneously performing direct phenotypic screening to isolate those mAbs with the most relevant biological activity, thus leading to the election of the best lead compounds for further development.

AgonOx’s approach to target discovery begins with genomic and proteomic analyses of tumor-
infiltrating lymphocytes isolated from human tumor biopsies. Candidates identified by these analyses are further validated using in-vitro assays and predictive in vivo murine cancer models. Andrew Weinberg, President of AgonOx, said "Collaborating with Invenra strengthens our efforts to develop immuno-oncology drug candidates through their novel antibody platform and complements our mission of discovering and delivering science that can change the standard of care for patients with cancer. Invenra has first-rate scientists that we hope to work with for years to come."

Roland Green, CEO and president of Invenra, said, "This collaboration is a major milestone for Invenra as a company and a validation of our innovative technology. We are delighted to be collaborating with the excellent team at AgonOx to identify best-in-class antibodies against their novel immuno-oncology target. In addition, this collaboration with AgonOx fits well within our business model, whereby we are partnering with a select group of companies while continuing to develop our own internal proprietary pipeline of therapeutic product candidates."

On December 13, 2016 MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, as well as autoimmune disorders and infectious diseases, reported an update on several of the Company’s product candidates and technology platforms (Press release, MacroGenics, DEC 13, 2016, View Source [SID1234517060]).

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"At today’s R&D Day, MacroGenics highlighted the continued progress our team is making to advance our growing portfolio of potential treatment options for patients with cancer, autoimmune disorders and infectious diseases," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "Today, we reviewed our expanded strategy for pursuing a balanced approached across novel and validated targets to develop three immuno-oncology franchises centered around HER2, B7-H3 and PD-1. This approach underscores our belief that cancer patients may significantly benefit from combinatorial and multi-specific strategies that are directly addressed by our core scientific expertise in creating and developing antibody, DART and TRIDENT therapeutics. The promising updates we provided on 11 of our programs today underscore the potential of our approach."

Program Updates and Highlights:

HER2 Franchise. MacroGenics provided an update regarding its most advanced franchise targeting the human epidermal growth factor receptor 2, or HER2, led by margetuximab, its Fc-optimized monoclonal antibody:

Phase 3 Metastatic Breast Cancer Study. The pivotal SOPHIA study is evaluating the efficacy of margetuximab plus chemotherapy compared to trastuzumab plus chemotherapy in approximately 530 relapsed/refractory HER2-positive metastatic breast cancer patients. MacroGenics today confirmed that it expects to complete enrollment of this study by late 2018.
Phase 2 Gastric Cancer Combination of Margetuximab with Anti-PD-1 mAb. The Company presented initial clinical data from a Phase 1b/2 trial of margetuximab in combination with an anti-PD-1 monoclonal antibody (pembrolizumab) in advanced HER2-positive gastric and gastroesophageal junction cancer patients. Preliminary data from the dose escalation portion of the study includes patients with objective response following progression on previous lines of treatment with trastuzumab and chemotherapy.
Pre-Clinical DART Program. MacroGenics presented preliminary non-clinical data from a DART program designed to engage both HER2 and CD137 (4-1BB), a costimulatory molecule, allowing for tumor-targeted immune cell activation.
B7-H3 Franchise. MacroGenics highlighted its industry-leading franchise related to the therapeutic targeting of B7-H3, a member of the B7 family of molecules involved in immune regulation, that is broadly expressed in multiple solid tumors:

Enoblituzumab. The Company provided clinical updates on ongoing monotherapy and combination studies with enoblituzumab, an Fc-optimized monoclonal antibody. In the Phase 1 monotherapy study, the antibody continues to be well-tolerated and the most promising activity to-date has been observed in prostate, bladder and post-checkpoint melanoma patients, consistent with what has been previously reported. Combination studies of enoblituzumab with either an anti-CTLA-4 mAb (ipilimumab) or anti-PD-1 mAb (pembrolizumab) indicate a manageable safety profile to date as well as initial signs of antitumor activity.
MGD009. MacroGenics presented initial data from the ongoing Phase 1 dose escalation study of MGD009, a bispecific B7-H3 x CD3 DART molecule. Adverse events have been manageable to date and initial signs of antitumor activity have been observed in three patients with triple negative breast cancer, renal cell carcinoma and mesothelioma.
MGC018. The Company introduced MGC018, an anti-B7-H3 antibody drug conjugate (ADC) based on a duocarmycin payload with cleavable peptide linker licensed from Synthon Biopharmaceuticals. The Company plans to submit an Investigational New Drug (IND) application for MGC018 in 2018.
PD1-Directed Immuno-Oncology Franchise. MacroGenics introduced several new programs in its pipeline directed towards PD-1, which will enable both a broad set of combination opportunities across its portfolio and further differentiation from existing PD-1-based treatment options:

MGA012. The Company introduced MGA012, an anti-PD-1 monoclonal antibody that recently began a Phase 1 clinical study. With anti-PD-1 therapy becoming a mainstay of cancer treatment across multiple tumors, MacroGenics believes this molecule will be the basis for combination therapy with several of its proprietary molecules.
MGD013. MacroGenics is developing MGD013 to provide co-blockade of two immune checkpoint molecules expressed on T cells, PD-1 and LAG-3, for potential treatment of diseases spanning a range of solid tumors as well as hematological malignancies. The Company has observed synergistic immunoregulatory activity in vitro, demonstrating that co-blockade with a PD-1 x LAG-3 DART molecule exceeds the effects achieved by combining two separate antibodies against these targets. The Company is completing IND-enabling studies and plans to submit an IND for MGD013 in the first half of 2017.
PD-1 x CTLA-4 Program. MacroGenics is developing a multi-specific therapeutic to address the co-blockade of PD-1 and CTLA-4, two clinically validated co-inhibitory molecules expressed on T cells.
Update on DART Clinical Programs. Across its portfolio of clinical DART programs, the Company highlighted the promising features of its DART platform, including on-target engagement, manageable safety and preliminary evidence of biological activity. These DART programs include MGD009 and the following:

MGD006. MacroGenics presented elements of its initial clinical experience from the ongoing Phase 1 dose escalation study of MGD006, a CD123 x CD3 DART molecule, in patients with AML (acute myeloid leukemia) or MDS (myelodysplastic syndrome). Supportive care regimens have been refined to enable significant limitations in the severity of cytokine release syndrome (CRS). In addition, the Company has characterized predictable pharmacokinetic properties of MGD006 and established biological and preliminary clinical activity in AML patients. The Company is now recruiting patients with AML or MDS in the U.S. and Europe.
MGD007. MacroGenics presented its initial clinical experience from the ongoing Phase 1 dose escalation study of MGD007, a gpA33 x CD3 DART, in patients with primary and metastatic colorectal cancers. In this study, gastrointestinal and constitutional symptoms have been reversible and consistent with the known target distribution of gpA33. Translational findings to date have included dose-dependent binding to CD4+ and CD8+ T cells in patients’ peripheral blood as well as histological demonstration of MGD007 binding to tumor cells in tumor biopsy specimens.

MGD010. The Company presented data from the fully enrolled Phase 1 study of MGD010, a CD32B x CD79B DART molecule, being developed for potential treatment of autoimmune disorders. MGD010 was well tolerated in healthy subjects in the single ascending dose study. In addition, MGD010 was shown to down-modulate B-cell function at multiple levels and preliminary data indicated that MGD010 was able to inhibit antibody response to Hepatitis A vaccination, providing clinical evidence consistent with the molecule’s expected mechanism of action.

On December Moleculin Biotech, Inc., (NASDAQ: MBRX) ("Moleculin" or the "Company"), a preclinical pharmaceutical company focused on the development of anti-cancer drug candidates, many of which are based on license agreements with The University of Texas System on behalf of the M.D. Anderson Cancer Center, reported its scientific presentation at the 28th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics (Press release, Moleculin, DEC 13, 2016, View Source [SID1234517062]). Waldemar Priebe, PhD, Moleculin’s Founder, Founding Scientist, and Chair of the Scientific Advisory Board presented the Abstract on November 30th at the Symposium in Munich, Germany.

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Wally Klemp, Chairman and CEO stated, "This presentation shows proof of concept data for our WP1122 portfolio, including data demonstrating increased survival of animals with human brain tumors treated with WP1122, as well as its biodistribution and pharmacokinetics. In non-optimal doses and treatment regimens, our lead inhibitor WP1122 performed equal to or better than the current market leader, cytotoxic drug temozolomide and significantly improved survival in animals treated with WP1122 in combination with temozolomide."

The following is an overview of the presentation, titled "Latentiation of 2-deoxy-D-glucose". No curative therapy exists for patients with high-grade malignant gliomas (GBMs). New approaches to the treatment of this disease are currently being evaluated with mixed results. One approach, that deserves to be therapeutically exploited, is targeting brain tumor metabolism. 2-Deoxy-D-glucose (2-DG), a known effective inhibitor of glycolysis, has been clinically tested but results did not meet expectations due to poor drug-like characteristics and inability to achieve therapeutic concentrations of 2-DG in the brain.

Dr. Waldemar Priebe stated, "We proposed to use latentiation of 2-DG to overcome this problem by chemically modifying biologically active 2-DG to form prodrugs with increased brain uptake that will be able to liberate in vivo the parent compound 2-DG in the brain. In our approach, we synthesized a series of differentially acetylated derivatives of 2-DG. Preliminary in vivo studies in mice of selected diacetates of 2-DG demonstrated >9 fold increased levels of 2-DG in the brain when compared with levels of 2-DG after administration of equimolar amount of 2-DG itself. Ultimately, our studies focused on a single compound 3,6-di-O-acetyl-2-deoxy-D-glucose (WP1122)."

Compound WP1122 was administered in vivo without toxic death up to the highest feasible dose of 3.0 g/kg intravenously and orally up to 6.0 g/kg. Significantly increased survival, comparable to or better than that of temozolomide, was observed for orally administered WP1122 in a U87 orthotopic glioma model at a dose of 1.25 g/kg. These promising results prompted continuation of preclinical toxicology evaluation of WP1122 aimed at the initiation of formal IND enabling studies. In addition, the proof of concept delivered by WP1122 has provided not only an effective approach to develop novel agents able to effectively cross the blood brain barrier but also a method to create a new class of dual function prodrugs by exploring biologically active acids.

Moleculin’s Chairman and CEO, Walter Klemp, concluded, "We are excited to present our results at this prestigious symposium. Clearly, the significantly increased survival data is key, especially as no curative therapy exists for patients with high-grade malignant gliomas today. We look forward to presenting additional data as we progress toward our clinical timeline."
For more information on the Symposium click: View Source

On December 13, 2016 CytomX Therapeutics, Inc. (Nasdaq:CTMX), a biopharmaceutical company developing investigational Probody therapeutics for the treatment of cancer, reported that Bristol-Myers Squibb Company has selected a clinical candidate for its CTLA-4 Probody program under the strategic oncology collaboration established in May 2014. Achieving this milestone results in a $2 million payment to CytomX (Press release, CytomX Therapeutics, DEC 13, 2016, View Source;p=irol-newsArticle&ID=2229234 [SID1234517063]).

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"Selecting a candidate for the CTLA-4 Probody program is a pivotal development in our partnership with CytomX Therapeutics and builds on our I.O. leadership," said Carl Decicco, Ph. D., Head of Discovery at Bristol-Myers Squibb. "We are studying the CTLA-4 Probody for its potential to deliver a next-generation anti-CTLA-4 therapy as we continue to explore transformational immuno-oncology medicines."

CTLA-4, a clinically validated inhibitory immune checkpoint protein, is the most advanced target from the companies’ collaboration, which now also includes three additional, unnamed targets in discovery.

"Advancing our CTLA-4 Probody program to clinical candidate stage with Bristol-Myers Squibb underscores the potential of the Probody platform to transform the field of immuno-oncology by delivering safer, more effective therapies," said Sean McCarthy, D.Phil., President and Chief Executive Officer of CytomX. "This partnership milestone, taken together with CytomX’s recently filed Investigational New Drug application for CX-072, a wholly owned PD-L1-directed Probody therapeutic, highlights the potential of our innovative platform to deliver a new generation of anti-cancer treatments."

About the Collaboration Agreement
Under the terms of the May 2014 agreement, CytomX granted Bristol-Myers Squibb exclusive worldwide rights to discover, develop and commercialize Probody therapeutics for up to four oncology targets. Bristol-Myers Squibb made an upfront payment of $50 million to CytomX in 2014, and is providing research funding over the course of the research term. Upon the selection of the third and fourth targets, Bristol-Myers Squibb paid CytomX selection payments. CytomX is also eligible to receive additional preclinical payments and up to $298 million in development, regulatory and sales milestone payments for each collaboration targe

On December 12, 2016 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that the results of an interim analysis of a global Phase Ib/II clinical study (Study 218) of its in-house discovered and developed anticancer agent eribulin mesylate (halichondrin class microtubule dynamics inhibitor, product name: Halaven, "eribulin") in combination with the anti-PD-1 antibody pembrolizumab developed by Merck & Co., Inc., Kenilworth, NJ, USA (known as MSD outside the U.S. and Canada), in patients with metastatic triple-negative breast cancer have been presented at the 39th Annual San Antonio Breast Cancer Symposium held from December 6 to 10, 2016 (Press release, Eisai, DEC 12, 2016, View Source [SID1234517039]). Development of this combination regimen is being conducted jointly under the cooperation of both companies.

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Study 218 is a Phase Ib/II clinical study which examined the activity and safety of eribulin in combination with pembrolizumab in 95 patients with metastatic triple-negative breast cancer previously treated with 0 – 2 lines of chemotherapy in the metastatic setting. The primary objective of the Phase Ib part was safety and tolerability, and the primary objective of the Phase II part was objective response rate (ORR).

This presentation reported on the results of an interim analysis of 39 evaluable patients out of the 89 patients enrolled in the study as of July 2016. Eribulin (1.4 mg/m2 intravenously on Day 1 and Day 8) and pembrolizumab (200 mg intravenously on Day 1) were administered to patients over 21 day cycles. From the results of the study, ORR was 33.3% (1 patient experienced a complete response and 12 patients experienced a partial response). In addition, the ORR was similar between PD-L1 positive and negative cohorts.

In this study, the most common treatment-emergent adverse events (incidence greater than or equal to 35%) in patients treated with the combination regimen were fatigue, nausea, peripheral neuropathy, neutropenia and alopecia, with Grade 3 or higher Treatment-Emergent Adverse Events (TEAEs) observed in 66.7% of patients. The most common Grade 3 or higher TEAEs (incidence greater than or equal to 7%) observed were neutropenia (30.8%) and fatigue (7.7%).

Eribulin is a halichondrin class microtubule dynamics inhibitor with a novel mechanism of action. Recent non-clinical studies showed that eribulin is associated with increased vascular perfusion and permeability in tumor cores.1 Eribulin promotes the epithelial state and decreases the capacity of breast cancer cells to migrate and invade.2 It was first approved for use in the treatment of metastatic breast cancer in the United States in November 2010, and is currently approved for use in the treatment of patients with breast cancer in over 60 countries including Japan and countries in Europe, the Americas and Asia.

Eisai positions oncology as a key therapeutic area, and is aiming to discover revolutionary new medicines with the potential to cure cancer. As exemplified by this combination regimen, Eisai remains committed to providing further clinical evidence for eribulin aimed at maximizing value of the drug as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers.

*Please refer to the following notes for the approved indications in the United States, Japan and Europe

Media Inquiries:
Public Relations Department,
Eisai Co., Ltd.
+81-(0)3-3817-5120

< Notes to editors >

1. About eribulin mesylate (product name: Halaven, "eribulin")
Eribulin is a halichondrin class microtubule dynamics inhibitor with a novel mechanism of action. Structurally, eribulin is a simplified and synthetically produced version of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai. Eribulin is believed to work by inhibiting the growth phase of microtubule dynamics which prevents cell division. In addition, recent non-clinical studies showed that eribulin is associated with increased vascular perfusion and permeability in tumor cores.1 Eribulin promotes the epithelial state and decreases the capacity of breast cancer cells to migrate and invade.2

Eribulin was first approved for use in the treatment of metastatic breast cancer in the United States in November 2010. Eribulin is currently approved for use in the treatment of breast cancer in over 60 countries worldwide, including Japan and countries in Europe, the Americas and Asia.
Furthermore, eribulin was first approved as a treatment for liposarcoma in the United States in January 2016, and is also approved for liposarcoma in countries in Europe and soft tissue sarcoma in Japan.

Specifically, eribulin is approved for the following indications.
In the United States for the treatment of patients with:
Metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.
Unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen.
In Japan for the treatment of patients with:
Inoperable or recurrent breast cancer
Soft tissue sarcoma
In Europe for the treatment of adult patients with:
Locally advanced or metastatic breast cancer who have progressed after at least one chemotherapeutic regimen for advanced disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting, unless patients were not suitable for these treatments.
Unresectable liposarcomas who have received prior anthracycline containing therapy (unless unsuitable) for advanced or metastatic disease.
2. About the Phase Ib/II Study (Study 218)
Study 218 is a multicenter, single-arm, open-label Phase 1b/II clinical study which examined the activity and safety of eribulin in combination with pembrolizumab in 95 patients (12 patients for the Phase Ib part, 83 patients for the Phase II part) with metastatic triple-negative breast cancer previously treated with 0-2 lines of chemotherapy in the metastatic setting. Eribulin (1.4 mg/m2 intravenously on Day 1 and Day 8) and pembrolizumab (200 mg intravenously on Day 1) were administered to patients over 21 day cycles. The primary objective of the Phase Ib part was safety and tolerability, and the primary objective of the Phase II part was ORR. Progression-free survival was assessed as a secondary objective.

In this interim analysis of 39 patients, 22 patients were previously treated with 1 to 2 lines of chemotherapy in the metastatic setting. The ORR was similar between PD-L1 positive (17 patients, ORR 29.4%) and negative (18 patients, ORR 33.3%) cohorts and it was 50% for PD-L1 unknown cohorts. Pembrolizumab alone demonstrated the tendency to increase the antitumor activity with PD-L1 positive in triple-negative breast cancer patients (KEYNOTE-012 study)3
In this study, eribulin in combination with pembrolizumab is expected to show similar antitumor activity regardless of PD-L1 status.

3. About triple-negative breast cancer
Triple-negative breast cancer is a type of breast cancer where the cancer cells tested negative for expression of estrogen receptors, progesterone receptors and HER-2 receptors. Since the tumor cells lack the necessary receptors, common treatments like hormone therapy and drugs that target HER-2 are ineffective. This remains a disease with significant unmet medical need. Therefore, the development of new medicines is necessary to advance the treatment of triple-negative breast cancer.

4. About non-clinical research related to the mechanism of action for eribulin in combination with pembrolizumab
Eribulin contributes to maintaining or increasing the activity of cytotoxic T lymphocytes (CTLs), which play a leading role in attacking cancer cells, via reduction of immune suppressive Treg cells and M2 tumor macrophages4. The anti-PD-1 antibody pembrolizumab maintains or activates CTLs via its immune-checkpoint blockade. Eribulin in combination with pembrolizumab is expected to work synergistically in cancer immunotherapy.