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Adimab Announces Antibody Discovery Collaboration with Takeda

On April 26, 2016 Adimab LLC, the global leader in the discovery and optimization of fully human monoclonal and bispecific antibodies, reported a multi-target partnership with Takeda Pharmaceutical Company Ltd. Under the terms of the agreement, Adimab will use its proprietary platform to discover and optimize antibodies against multiple targets chosen by Takeda, who will have the right to develop and commercialize therapeutic programs resulting from the collaboration (Press release, Adimab, APR 26, 2016, View Source [SID1234536592]).

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"We are pleased to be working with a company with such deep expertise in antibody discovery and engineering," stated Christopher Claiborne, Ph.D., Head of Oncology Discovery at Takeda. "Adimab’s breadth of technical offerings, including bispecifics, as well as their reputation in the industry enables us to continue fulfilling our mission of aspiring to cure cancer."

"We are excited to have Takeda as a partner, and we look forward to demonstrating Adimab’s advantages to the Takeda team," said Tillman Gerngross, Chief Executive Officer and Co-Founder of Adimab. "This partnership, like most of our initial partnerships, will focus on a handful of projects. Our goal is to have our partners see the output from the collaboration and fall in love with the platform. We are always happy to expand the initial collaboration into additional funded discovery projects, or even transfer the platform to our partner’s facilities – to date most of our partnerships have expanded in some way."

Under the terms of the agreement, Adimab will use its proprietary yeast-based discovery and optimization platform or its proprietary rapid B cell sorting capabilities to identify fully human antibodies and against selected targets. For each target, Adimab will grant Takeda the right to research antibodies generated during the collaboration for potential use in therapeutic products. Adimab will receive an undisclosed upfront payment, research fees and technical milestones. In addition, for each target Takeda will have the option to exclusively license antibodies generated during the collaboration as a therapeutic lead, for which Adimab would receive license fees, clinical milestones and royalties on product sales.

Over the past seven years, Adimab has established funded discovery collaborations with over 35 companies. With this collaboration, Takeda joins Adimab’s other large pharmaceutical funded discovery partners, including Novo Nordisk, Biogen, GSK, Roche, Novartis, Eli Lilly, Genentech, Celgene, Gilead, Kyowa Hakko Kirin, Sanofi and others. Adimab has also partnered with many mid-size and early-stage venture-backed companies, including Merrimack, Five Prime, Jounce, Innovent, Alector, Acceleron, Oncothyreon, Surface Oncology, Potenza, Arsanis and others, as well as academic institutions such as Memorial Sloan Kettering and MD Anderson. In addition to funded discovery programs, the Adimab antibody discovery and optimization platform and custom antibody libraries have been transferred to Merck, Novo Nordisk, Biogen and GSK for internal use.

Zymeworks and GSK Enter Second Strategic Collaboration to Develop and Commercialize Bi-Specific Antibodies

On April 26, 2016 Zymeworks Inc., a leader in the development of bi-specific and multi-specific antibodies and antibody drug conjugates, reported that it has entered into a new licensing agreement with GSK for the research, development, and commercialization of novel bi-specific antibodies enabled using Zymeworks’ Azymetric drug discovery platform (Press release, Zymeworks, APR 26, 2016, View Source [SID1234536466]). Under the agreement, GSK will have the option to develop and commercialize multiple bi-specific drugs across different disease areas. Zymeworks will receive upfront and preclinical payments of up to USD$36 million and is eligible to receive up to USD$152 million in development and clinical milestone payments, along with commercial sales milestone payments of up to USD$720 million, and tiered royalties on potential sales.

As previously announced in December 2015, Zymeworks and GSK entered into a collaboration and license agreement to further develop Zymeworks’ Effector Function Enhancement and Control Technology (EFECT) platform and to research, develop, and commercialize novel Fc-engineered monoclonal and bi-specific antibody therapeutics that have been optimized for specific therapeutic effects. As part of this second agreement, GSK has also gained the right to combine the Azymetric platform with novel engineered Fc domains developed under the previously announced collaboration.

"We are excited to be expanding our relationship with GSK to include our Azymetric bi-specific platform. We view this new collaboration as evidence of our valuable role as a partner and the strength of our proprietary drug development platforms," said Ali Tehrani, Ph.D., President and CEO of Zymeworks. "The proceeds from this collaboration will be used to advance our pipeline of therapeutic candidates, including the Azymetric antibody ZW25 and the Azymetric antibody drug conjugate ZW33, into human clinical trials this year. They will also be utilized to support the continued expansion and strengthening of our core capabilities in antibody discovery, protein engineering, and antibody drug conjugates."

About the Azymetric Platform
Bi-specific antibodies developed using the Azymetric platform resemble conventional mono-specific antibodies while being able to simultaneously bind to two different targets resulting in additive or synergistic therapeutic responses. Azymetric antibodies spontaneously assemble into a single molecule with two different Fab domains comprising of unique heavy and light chain pairings. Azymetric antibodies are manufactured using conventional monoclonal antibody processes and can also be easily adapted to rapidly screen target and sequence combinations for bi-specific activities in the final therapeutic format thereby significantly reducing drug development timelines.

About the EFECT Platform
The EFECT platform is a library of antibody Fc modifications engineered to modulate the activity of the antibody-mediated immune response, which includes both the up and down-regulation of effector functions. This platform is compatible with traditional monoclonal as well as Azymetric bi-specific antibodies to further enable the customization of therapeutic responses for different diseases.

Three Year Follow up of GMCSF/bi-shRNA(furin) DNA Transfected Autologous Tumor Immunotherapy (Vigil(™)) in Metastatic Advanced Ewing’s Sarcoma.

Ewing’s sarcoma is a devastating rare pediatric cancer of the bone. Intense chemotherapy temporarily controls disease in most patients at presentation but has limited effect in patients with progressive or recurrent disease. We previously described preliminary results of a novel immunotherapy, FANG(TM) (Vigil(TM)) vaccine, in which 12 advanced stage Ewing’s patients were safely treated and went on to achieve a predicted immune response (IFN? ELISPOT). We describe follow-up through year 3 of a prospective, non-randomized study comparing an expanded group of Vigil-treated advanced disease Ewing’s sarcoma patients (n=16) with a contemporaneous group of Ewing’s sarcoma patients (n=14) not treated with Vigil. Long-term follow up results show a survival benefit without evidence of significant toxicity (no = grade 3) to Vigil when administered once monthly by intradermal injection (1x10e(6) cells/injection to 1x10e(7) cells/injection). Specifically, we report a 1-year actual survival of 73% for Vigil treated patients compared to 23% in those not treated with Vigil. In addition, there was a 17.2 month difference in overall survival (OS; Kaplan-Meier) between the Vigil (median OS 731 days) and no Vigil patient groups (median OS 207 days). In conclusion, these results supply the rational for further testing of Vigil in advanced stage Ewing’s sarcoma.

MiR-130b ameliorates murine lupus nephritis through targeting type I interferon pathway on resident renal cells.

Type I Interferon (IFN) is a critical pathogenic factor during the progression of Lupus Nephritis (LN). Although microRNAs (miRNAs) have been shown to control IFN response in immune cells of LN, the role of miRNAs in resident renal cells remain unclear. Here, we investigated the role of miR-130b in IFN pathway in renal cells, and its therapeutic effect in LN.
Kidney tissues from patients and mouse model of LN were collected for detecting miR-130b levels. Primary renal mesangial cells (RMCs) were used to determine the role of miR-130b in IFN pathway. We overexpressed miR-130b by administrating miR-130b agomir in an IFNα-accelerated LN mouse model to test its therapeutic efficacy.
Downregulated miR-130b expression was observed in kidney tissues from patients and mouse model of LN. Further analysis showed that underexpression of miR-130b negatively correlated with abnormal activation of IFN response in LN patients. In vitro, overexpressing miR-130b suppressed the downstream of type I IFN pathway in RMCs by targeting interferon regulatory factor 1 (IRF1). The opposite effect was observed when inhibited internal miR-130b expression. The inverse correlation between IRF1 and miR-130b levels was detected in renal biopsies from LN patients. More importantly, in vivo administration of miR-130b agomir reduced IFNα-accelerated LN progression, including decreased proteinuria, lower levels of complexes deposition and lack of glomeruli lesion.
miR-130b is a novel negative regulator of type I IFN pathway in renal cells. Overexpression of miR-130b in vivo ameliorates IFNα-accelerated LN, providing potential novel strategies for LN therapeutic intervention. This article is protected by copyright. All rights reserved.
© 2016, American College of Rheumatology.

Metabolism of AM404 From Acetaminophen at Human Therapeutic Dosages in the Rat Brain.

Acetaminophen, an analgesic and antipyretic drug, has been used clinically for more than a century. Previous studies showed that acetaminophen undergoes metabolic transformations to form an analgesic compound, N-(4-hydroxyphenyl) arachidonamide (AM404), in the rodent brain. However, these studies were performed with higher concentrations of acetaminophen than are used in humans.
The aim of the present study was to examine the metabolism of AM404 from acetaminophen in the rat brain at a concentration of 20 mg/kg, which is used in therapeutic practice in humans, and to compare the pharmacokinetics between them.
We used rat brains to investigate the metabolism of AM404 from acetaminophen at concentrations (20 mg/kg) used in humans. In addition, we determined the mean pharmacokinetic parameters for acetaminophen and its metabolites, including AM404.
The maximum plasma concentrations of acetaminophen and AM404 in the rat brain were 15.8 µg/g and 150 pg/g, respectively, with corresponding AUC0-2h values of 8.96 μg hour/g and 117 pg hour/g. The tmax for both acetaminophen and AM404 was 0.25 hour.
These data suggest that AM404’s concentration-time profile in the brain is similar to those of acetaminophen and its other metabolites. Measurement of blood acetaminophen concentration seems to reflect the concentration of the prospective bioactive substance, AM404.