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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

JNJ-63709178, a bispecific antibody that targets CD3 and CD123, was created under a collaboration between Genmab and Janssen using Genmab’s DuoBody technology (Company Pipeline, Genmab, APR 26, 2016, View Source [SID:1234511406]). JNJ-63709178 is being investigated in a Phase I clinical study to treat relapsed or refractory acute myeloid leukemia and is the second bispecific antibody created with the DuoBody technology to be added to Genmab’s pipeline.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

To assess sirukumab, an anti-interleukin-6 monoclonal antibody, for treatment of active lupus nephritis (LN).
Patients with Class III or IV LN (renal biopsy within 14 months of randomization), persistent proteinuria (≥0.5 g/d) despite immunosuppression, and stable renin-angiotensin system blockade were randomized (5:1) to receive intravenous sirukumab 10 mg/kg (n=21) or placebo (n=4) every 4 weeks through week 24. The primary endpoint was percent reduction of proteinuria (measured as the protein/creatinine ratio in a 12-hour urine collection) from baseline to week 24.
Twenty-five patients were enrolled; 19 (76.0%) completed treatment through week 24, and 6 (24.0%) discontinued the study agent early, 5 due to adverse events. At week 24, the median percent change in proteinuria from baseline in sirukumab-treated patients was 0.0% (95% CI: -61.8, 39.6). In contrast, the 4 placebo patients showed a median percent increase in proteinuria of 43.3% at week 24. Of note, a subset of 5 sirukumab-treated patients had ≥50% improvement in their protein/creatinine ratio through week 28. In the sirukumab group, 47.6% of patients had ≥1 serious adverse event; most were infection-related. No deaths or malignancies occurred. No serious adverse events were observed in the four placebo-treated patients.
This proof-of-concept study did not demonstrate the anticipated efficacy or an acceptable safety profile following sirukumab treatment in this population of patients with active LN receiving concomitant immunosuppressive treatment. This article is protected by copyright. All rights reserved.
© 2016, American College of Rheumatology.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On April 26, 2016 Tokai Pharmaceuticals Inc. (NASDAQ: TKAI), a biopharmaceutical company focused on developing and commercializing innovative therapies for prostate cancer and other hormonally driven diseases, reported an oral presentation on galeterone at the 2016 American Urological Association (AUA) Annual Meeting in San Diego (Press release, Tokai Pharmaceuticals, APR 26, 2016, View Source;p=RssLanding&cat=news&id=2161338 [SID:1234511407]). Galeterone, Tokai’s lead product candidate, is being developed for the treatment of men with metastatic castration-resistant prostate cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The presentation, titled "Galeterone shows anti-tumor activity in multiple pre-clinical models that express androgen receptor splice variants, supporting correlative patient data seen in ARMOR2" (abstract number PD32-07), will be presented on Sunday, May 8, from 4:30 – 4:40 p.m. PDT in room 30DE, as part of the session, "Prostate Cancer: Advanced (including Drug Therapy) III." The presenting author is Vincent C.O. Njar, Ph.D., Professor of Medicinal Chemistry and Pharmacology, Department of Pharmacology; Head of the Medicinal Chemistry Section, Center for Biomolecular Therapeutics; and Member of the Marlene and Stewart Greenebaum Cancer Center at the University of Maryland School of Medicine, Baltimore. Dr. Njar is a co-inventor of galeterone.

Additional information, including the presentation schedule and full abstracts, may be found at www.aua2016.org. A copy of the presentation will be available on the "Publications & Presentations" page of Tokai’s website, www.tokaipharmaceuticals.com.

About Galeterone
Galeterone is an oral small molecule that utilizes the established pathways, including CYP17 enzyme and androgen receptor inhibition, of the current second-generation hormonal therapies abiraterone and enzalutamide. Galeterone also introduces a distinct third mechanism – androgen receptor degradation – that decreases the sensitivity of androgen receptors to androgen activity, thus leading to reductions in tumor growth. Tokai is developing galeterone for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). ARMOR3-SV, the company’s pivotal Phase 3 study of galeterone in treatment-naive mCRPC patients whose prostate tumors express the AR-V7 splice variant, is evaluating whether administration of galeterone results in a statistically significant increase in radiographic progression-free survival as compared to enzalutamide. Tokai is also evaluating galeterone in mCRPC patients who have shown resistance following treatment with second-generation hormonal agents. Tokai has worldwide development and commercialization rights to galeterone.

Veno-occlusive disease (VOD) is an early and serious complication of hematopoietic cell transplantation (HCT) that is associated with inferior survival, particularly when it is complicated by multi-organ failure (severe VOD). We evaluated the efficacy of defibrotide in the treatment of severe VOD using observational data from the Center for International Blood and Marrow Transplant Research (CIBMTR). Eight thousand three hundred forty-one patients treated by HCT between 2008 and 2011 were identified from the CIBMTR clinical database; 3.2% met criteria for VOD and 1.2% met criteria for severe VOD. Patients with a diagnosis of VOD as reported to the CIBMTR by their transplanting centers, who had no prior history of cirrhosis, and who had a maximum total bilirubin >2.0mg/dl by day +100 post-HCT were selected for study. Severe VOD was defined as VOD occurring in the setting of renal impairment requiring dialysis or any non-infectious pulmonary abnormality. Patients with severe VOD were divided into two groups for analysis: those treated with defibrotide (n=41) and those not treated with defibrotide (n=55). Patients in the non-defibrotide group were older, were more likely to be male, were more likely to have a history of previous fungal infection, and had a higher proportion of clinically significant pre-existing disease or organ impairment. Survival at day +100 was 39% (95% CI: 24.8-54.3%) in patients receiving defibrotide and 30.9% (95% CI: 19.5% – 43.6%) in those not receiving defibrotide. Resolution of VOD at day +100 was 51% in the defibrotide group, and 29% in the non-defibrotide group (difference 22.1%, 95% CI: 2.6% – 42%). The results of our study are consistent with previously reported experiences with defibrotide, confirm the poor outcome of this syndrome, and suggest defibrotide is effective in the treatment of severe VOD.
Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!