Cardiovascular disease (CVD) is the leading cause of death worldwide and new approaches for both diagnosis and treatment are required. Autoantibodies directed against apolipoprotein A-I (ApoA-I) represent promising biomarkers for use in risk stratification of CVD and may also play a direct role in pathogenesis.
To characterize the anti-ApoA-I autoantibody response, we measured the immunoreactivity to engineered peptides corresponding to the different alpha-helical regions of ApoA-I, using plasma from acute chest pain cohort patients known to be positive for anti-ApoA-I autoantibodies.
Our results indicate that the anti-ApoA-I autoantibody response is strongly biased towards the C-terminal alpha-helix of the protein, with an optimized mimetic peptide corresponding to this part of the protein recapitulating the diagnostic accuracy for an acute ischemic coronary etiology (non-ST segment elevation myocardial infarction and unstable angina) obtainable using intact endogenous ApoA-I in immunoassay. Furthermore, the optimized mimetic peptide strongly inhibits the pathology-associated capacity of anti-ApoA-I antibodies to elicit proinflammatory cytokine release from cultured human macrophages.
In addition to providing a rationale for the development of new approaches for the diagnosis and therapy of CVD, our observations may contribute to the elucidation of how anti-ApoA-I autoantibodies are elicited in individuals without autoimmune disease.

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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.

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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.

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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.

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.

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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.