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Source: Amgen and reported by http://www.prnewswire.com/
THOUSAND OAKS, Calif., Sept. 27, 2016 /PRNewswire/ -- Amgen (NASDAQ: AMGN) today announced top-line results of the Phase 3 CLARION trial, which evaluated an investigational regimen of KYPROLIS® (carfilzomib), melphalan and prednisone (KMP) versus Velcade® (bortezomib), melphalan and prednisone (VMP) for 54 weeks in patients with newly diagnosed multiple myeloma who were ineligible for hematopoietic stem-cell transplant. The trial did not meet the primary endpoint of superiority in progression-free survival (PFS) (median PFS 22.3 months for KMP versus 22.1 months for VMP, HR = 0.91, 95 percent CI, 0.75 - 1.10). While the data for overall survival, a secondary endpoint, are not yet mature, the observed hazard ratio (KMP versus VMP) was 1.21 (95 percent CI, 0.90 - 1.64). Neither result was statistically significant.

Overall, the adverse events in the KMP arm were consistent with the known safety profile of KYPROLIS. The incidence of Grade 3 or higher adverse events was 74.7 percent in the KMP arm and 76.2 percent in the VMP arm. Fatal treatment-emergent adverse events occurred in 6.5 percent of KMP patients and 4.3 percent of VMP patients. The incidence of Grade 2 or higher peripheral neuropathy, a secondary endpoint, was 2.5 percent in the KMP arm and 35.1 percent in the VMP arm.
Read more: http://www.prnewswire.com/news-releases/amgen-announces-top-line-results-from-phase-3-kyprolis-carfilzomib-clarion-study-in-newly-diagnosed-multiple-myeloma-patients-300334540.html

Source: http://www.businesswire.com/
BEIJING--(BUSINESS WIRE)--CANbridge Life Sciences, a biopharmaceutical company focused on developing Western drug candidates in China and North Asia, announced that the first patient was dosed in the Phase I/II trial of its lead candidate, CAN-008, for the treatment of newly-diagnosed glioblastoma multiforme (GBM), in Taiwan. The patient was treated at Linkou Chang Gung Memorial Hospital, in Taipei, Taiwan. CAN-008, CANbridge’s lead candidate, is an immunotherapy that enhances the immune system response to cancer and inhibits tumor cell growth. The study design consists of an open-label, dose-escalation Phase I trial, and a multi-center, double-blind, randomized, placebo-controlled Phase II trial. The Phase I trial will evaluate safety, tolerability, pharmacokinetics and preliminary efficacy. The Phase II trial will evaluate efficacy and safety. The combined Phase I/II trial will enroll a total of 55 patients. CANbridge expects to report Phase I safety data after mid-2017.
“CANbridge is now a clinical stage company, delivering on our mission to develop Western drug candidates for Asian markets,” said James Xue, CANbridge CEO. “It is of particular value to us that CAN-008 shows promise in glioblastoma multiforme, a terrible cancer that has had no new front-line treatments approved, anywhere in the world, since 1999. We are proud to bring a potentially new treatment option to this underserved group of patients.”
Read more: http://www.businesswire.com/news/home/20160926005368/en/Patient-Dosed-CANbridge%E2%80%99s-CAN-008-Phase-III-Trial

Source: https://globenewswire.com/
PHILADELPHIA and HOUSTON, United States and OXFORD, United Kingdom, Sept. 26, 2016 (GLOBE NEWSWIRE) -- Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, and The University of Texas MD Anderson Cancer Center announced today that they have entered into a multi-year strategic alliance designed to expedite the development of novel adoptive T-cell therapies for multiple types of cancer.

The alliance pairs MD Anderson’s preclinical and clinical teams with Adaptimmune’s scientists and proprietary SPEAR® (Specific Peptide Enhanced Affinity Receptor) T-cell technology platform, which enables Adaptimmune to identify targets expressed on solid and hematologic cancers and to develop affinity enhanced T-cell receptors (TCRs) with optimal potency and specificity against them.

The teams will collaborate in a number of areas including preclinical and clinical development of Adaptimmune’s SPEAR T-cell therapies targeting MAGE-A10 and future clinical stage first and second generation SPEAR T-cell therapies such as MAGE-A4 across a number of cancers, including bladder, lung, ovarian, head and neck, melanoma, esophageal and gastric cancers. The alliance will also drive research and development of other new SPEAR TCR therapies to targets in other tumor types such as breast cancers and facilitate clinical study participation by MD Anderson in other Adaptimmune trials. Access to MD Anderson’s tumor repository will guide further target selection and clinical trial design, while its cancer immunology cores and expertise in performing translational medicine studies may help optimize the efficacy and safety of SPEAR T-cell therapies.
Read more: https://globenewswire.com/news-release/2016/09/26/874501/0/en/MD-Anderson-Cancer-Center-and-Adaptimmune-Form-Strategic-Alliance-to-Advance-Development-of-Immunotherapies-Targeting-Multiple-Cancers.html

Source: http://www.dgap.de/
Pamplona, Spain, 26. September 2016 - Cinfa Biotech S.L., the biosimilars company of Infarco group, today announced the start of the second clinical study with its lead development candidate B12019, a biosimilar version of Neulasta(R) (pegfilgrastim) to treat chemotherapy-induced neutropenia. The objective of the trial is to investigate the pharmacodynamics (PD) and immunogenicity of B12019 compared to Neulasta(R).
The multiple-dose, randomised, double-blind, cross-over study will enrol 96 healthy volunteers in Germany. Secondary endpoints of the trial include pharmacokinetic (PK) and safety parameters. The study design is based on scientific advice from the European Medicines Agency (EMA) and is tailored to the specific properties of pegfilgrastim.
Dr. Ruediger Jankowsky, Managing Director of Cinfa Biotech GmbH, commented: "The successful clinical trial of B12019, which we reported in July this year, allowed for the immediate continuation of the clinical development program, especially since proving that we have such a high-quality product and a confirmed development strategy. The timely start of the second clinical study marks an important milestone in the development of B12019."
Read more: http://www.dgap.de/dgap/News/corporate/cinfa-biotech-starts-second-clinical-study-pegfilgrastim-biosimilar-candidate-b/?newsID=963037

Source: Palatin Technologies, Inc. and reported by http://www.prnewswire.com/
CRANBURY, N.J., Sept. 23, 2016 /PRNewswire/ -- Palatin Technologies, Inc. (NYSE MKT: PTN), a biopharmaceutical company developing targeted, receptor-specific peptide therapeutics for the treatment of diseases with significant unmet medical need and commercial potential, announced that a review of the neurobiology and treatment efficacy of bremelanotide for hypoactive sexual desire disorder ("HSDD") was presented at the International Society for Sexual Medicine 20th World Meeting in Beijing, China.
Anita H. Clayton, M.D., of the University of Virginia School of Medicine, is lead author on the poster entitled "Bremelanotide: A Review of Its Neurobiology and Treatment Efficacy for HSDD." The poster addresses mechanisms of sexual response and the pathophysiology of HSDD, and describes the potential of bremelanotide to modulate brain pathways involved in sexual response.
James G. Pfaus, Ph.D., of Concordia University in Montreal, Canada was co-author, together with Johna Lucas, M.D., Carl Spana, Ph.D. and Robert Jordan of Palatin.
Palatin is developing bremelanotide, a centrally-mediated medication, as a subcutaneous, on-demand treatment for premenopausal women diagnosed with HSDD. Bremelanotide, which is a melanocortin 4 receptor agonist drug candidate, is a synthetic peptide analog of the naturally occurring hormone alpha-MSH (melanocyte-stimulating hormone).
Read more: http://www.prnewswire.com/news-releases/palatin-technologies-presents-bremelanotide-neurobiology-and-treatment-efficacy-review-at-world-meeting-on-sexual-medicine-300332936.html

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Source:

Angew Chem Int Ed Engl. 2016 Apr 18;55(17):5124-34. doi: 10.1002/anie.201508428. Epub 2016 Mar 16.

Abstract

Peptide-decorated dendrimers (PDDs) are a class of spherical, regular, branched polymers that are modified by peptides covalently attached to their surface. PDDs have been used as protein mimetics, novel biomaterials, and in a wide range of biomedical applications. Since their design and development in the late eighties, poly-l-lysine has been a preferred core structure for PDDs. However, numerous recent innovations in polymer synthesis and ligation chemistry have re-energized the field and led to the emergence of well-defined peptide dendrimers with more diverse core structures and functions. This Minireview highlights the development of PDDs driven by significantly improved ligation chemistry incorporating structurally well-defined peptides and the emerging use of PDDs in imaging and drug development.

Wan J¹, Alewood PF².

Author information

• ¹Institute of Molecular Bioscience, The University of Queensland, 306 Carmody Road, St Lucia, QLD 4072, Australia.
• ²Institute of Molecular Bioscience, The University of Queensland, 306 Carmody Road, St Lucia, QLD 4072, Australia. p.alewood@imb.uq.edu.au.

Source:

Angew Chem Int Ed Engl. 2016 Sep 14. doi: 10.1002/anie.201607188. [Epub ahead of print]

Abstract

Macrocyclic compounds have received increasing attention in recent years. With their large surface area, they hold promise for inhibiting protein-protein interactions, a chemical space that was thought to be undruggable. Although many chemical methods have been developed for peptide macrocyclization, enzymatic methods have emerged as a promising new economical approach. Thus far, most enzymes have been shown to act on l-peptides; their ability to cyclize d-amino-acid-containing peptides has rarely been documented. Herein we show that macrocycles consisting of d-amino acids, except for the Asn residue at the ligating site, were efficiently synthesized by butelase 1, an Asn/Asp-specific ligase. Furthermore, by using a peptide-library approach, we show that butelase 1 tolerates most of the d-amino acid residues at the P1'' and P2'' positions.

Nguyen GK¹, Hemu X¹, Quek JP¹, Tam JP².

Author information

• ¹School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.
• ²School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore. jptam@ntu.edu.sg.

Source:

J Am Chem Soc. 2016 Sep 21;138(37):12099-111. doi: 10.1021/jacs.6b03765. Epub 2016 Sep 8.

Abstract

A "D-scan" of two small proteins, the disulfide-rich Ecballium elaterium trypsin inhibitor II (EETI-II) and a minimized Z domain of protein A (Z33), is reported. For each protein, the stereochemistry of one amino acid at a time was inverted to generate a series of diastereomers. In much the same way an alanine scan determines necessary residues for protein function, the D-scan elucidated the critical stereocenters of the 30-residue EETI-II and the 33-residue Z33. The folding properties and activity of each variant were investigated. A total of 24 out of 30 EETI-II D-scan analogues folded to give a three-disulfide product. Of the 24 variants that folded, half were high-affinity trypsin inhibitors, and three were as active as the wild type (WT). Of these 12 active variants, most were substantially less stable to reduction than WT EETI-II (WT first reduction potential -270.0 ± 1.5 mV, WT second reduction potential -307.2 ± 1.1 mV). Similarly, ten Z33 analogues retained high binding affinity to IgG (KD < 250 nM, WT: 24 ± 1 nM) and 12 additional analogues had reduced but appreciable IgG binding affinity (KD between 250 nM and 2.5 μM). As with EETI-II, most Z33 analogues were substantially less stable than the WT (ΔG(H2O, 263 K) = 2.4 ± 1.2 kcal/mol). Collectively, our findings show that the D-scan is powerful new strategy for studying how the stereochemistry of amino acids affects the structure and function of proteins.

Simon MD¹, Maki Y^1,2, Vinogradov AA¹, Zhang C¹, Yu H³, Lin YS³, Kajihara Y², Pentelute BL¹.

Author information

• ¹Department of Chemistry, Massachusetts Institute of Technology , 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
• ²Department of Chemistry, Graduate School of Science, Osaka University , 1-1, Machikaneyama-cho, Toyonaka, Osaka 560-0043, Japan.
• ³Department of Chemistry, Tufts University , 62 Talbot Avenue, Medford, Massachusetts 02155, United States.