On April 22, 2016 Adaptimmune Therapeutics plc (NASDAQ:ADAP), a leader in the use of TCR engineered T-cell therapy to treat cancer, reported that the company has adopted the name SPEAR T-cells (Specific Peptide Enhanced Affinity Receptor T-cells) to describe its proprietary technology (Press release, Adaptimmune, APR 22, 2016, View Source;p=RssLanding&cat=news&id=2159628 [SID:1234511273]).

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The SPEAR T-cells brand is intended to symbolize the vital role that Adaptimmune’s enhanced affinity T-cell receptors play in targeting cancer.

Adaptimmune has a history of scientific leadership in the field of T-cell engineering and the company’s proprietary T-cell engineering platform, developed over the last 15 years, has generated a strong pipeline of T-cell therapies.

"Affinity optimized T-cell receptors are essential to the fight against cancer," said James Noble, Adaptimmune’s Chief Executive Officer. "Our SPEAR T-cell technology is unique in delivering correctly identified targets and enhanced affinity TCRs that have the potency needed to attack tumors, but also the optimum specificity to minimize risks of cross-reactivity. Our proprietary technology provides us with ‘supra-natural’ TCRs that enable the acceleration of our programs and also facilitates our development of second generation TCRs."

Stakeholders across the clinical trial enterprise have expressed concern that the current clinical trial enterprise is unsustainable. The cost and complexity of trials have continued to increase, threatening our ability to generate reliable evidence essential for making appropriate decisions concerning the benefits and harms associated with clinical interventions. Overcoming this inefficiency rests on improving protocol design, trial planning, and quality oversight.
The Clinical Trials Transformation Initiative convened a project to evaluate methods to prospectively build quality into the scientific and operational design of clinical trials ("quality-by-design"), such that trials are feasible to conduct and important errors are prevented rather than remediated. A working group evaluated aspects of trial design and oversight and developed the Clinical Trials Transformation Initiative quality-by-design principles document, outlining a series of factors generally relevant to the reliability of trial conclusions and to patient safety. These principles were then applied and further refined during a series of hands-on workshops to evaluate their utility in facilitating proactive, cross-functional dialogue, and decision-making about trial design and planning. Following these workshops, independent qualitative interviews were conducted with 19 workshop attendees to explore the potential challenges for implementing a quality-by-design approach to clinical trials. The Clinical Trials Transformation Initiative project team subsequently developed recommendations and an online resource guide to support implementation of this approach.
The Clinical Trials Transformation Initiative quality-by-design principles provide a framework for assuring that clinical trials adequately safeguard participants and provide reliable information on which to make decisions on the effects of treatments. The quality-by-design workshops highlighted the value of active discussions incorporating the different perspectives within and external to an organization (e.g. clinical investigators, research site staff, and trial participants) in improving trial design. Workshop participants also recognized the value of focusing oversight on those aspects of the trial where errors would have a major impact on participant safety and reliability of results. Applying the Clinical Trials Transformation Initiative quality-by-design recommendations and principles should enable organizations to prioritize the most critical determinants of a trial’s quality, identify non-essential activities that can be eliminated to streamline trial conduct and oversight, and formulate appropriate plans to define, avoid, mitigate, monitor, and address important errors.
© The Author(s) 2016.

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Monitoring of anti-drug antibodies (ADAbs) or serum concentrations of biologicals in treatment of rheumatoid arthritis could provide an explanation for a loss of efficacy and help in the choice of subsequent medication. Current clinical practices do not generally include such monitoring of tumor necrosis factor (TNF)-α blockers on a routine basis. The main aims of this study were to estimate the probabilities of optimal and nonoptimal treatment decisions if infliximab or adalimumab drug trough level (DL) and ADAbs are tested or not in rheumatoid arthritis, and to model cost-effectiveness of performing such monitoring on a routine basis. Data on DLs and ADAbs concentrations were obtained in Finland from clinically requested monitoring analyses of 486 and 1,137 samples from patients on adalimumab and infliximab, respectively. DL was within the target range in 42% of samples from adalimumab- and 50.4% of infliximab-treated patients. ADAbs were detected in approximately 20% and 13.5% of samples from adalimumab- and infliximab-treated patients, respectively. ADAbs were found in 52.3% and 41.3% of those with low adalimumab or infliximab DLs, respectively. The monitoring data were incorporated into probabilities for making the optimal treatment decision. Economic impact of clinical decision-making was modeled in a short-term (3-6 months) scenario with 100 hypothetical patients. In the model, the combined measurement of DLs and ADAbs was cost-saving compared to the nontesting scenario when the monitoring results affected the treatment decision in at least 2-5 of 100 patients, a proportion which is easily exceeded in real-life clinical practice. This study indicates that routine monitoring of drug level and ADAbs is cost-beneficial in clinical practice, thereby improving the decision-making process in using TNF-α blockers.

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On April 22, 2016 Alligator Bioscience AB is a privately held Swedish biotech company developing immuno-oncology antibodies for directed immunotherapy of cancer (Press release, Alligator Bioscience, APR 22, 2016, View Source [SID1234538693]). Alligator reported that it granted Johnson & Johnson an exclusive, worldwide license to Alligator’s clinical candidate ADC-1013 in an agreement entered in August 2015.

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According to this agreement, Janssen will be responsible for developing ADC-1013 and will assume responsibility for the clinical studies once the ongoing, by Alligator sponsored Phase I dose escalation study is completed. Janssen will have exclusive rights to develop and commercialize ADC-1013 initially targeting a number of solid tumors and hematological cancers and will assume responsibility for all additional research, development, manufacturing, regulatory and commercialization activities.
There has been an amendment of the protocol to expand the current Phase I Clinical Study to include a systemic administration arm. This entitles Alligator to a milestone payment of USD 5M.
Separately Janssen and Alligator have also entered a research collaboration to broaden the pre-clinical data package of ADC-1013. Janssen will reimburse Alligator for 2.5 FTEs and running expenses under this agreement.
"It is very encouraging for the ADC-1013 project and the ongoing Phase I studies that the trials are progressing extremely well and are being expanded by a systemic administration arm. This will give us and our partner Janssen important information for the future development of ADC-1013" said Per Norlén CEO at Alligator Bioscience.

For further information, please contact:
Per Norlén, CEO Alligator Bioscience AB, Office number: +46 46 2864280

About ADC-1013
ADC-1013 is an agonistic fully human monoclonal antibody targeting CD40, an immuno-stimulatory receptor found on antigen-presenting cells such as dendritic cells. Stimulation of CD40 on dendritic cells initiates a process leading to a dramatic increase in T effector cells attacking the tumor. In addition, a tumor-specific memory is established, leading to long-term immunity to the cancer.

This press release contains forward-looking statements, consisting of subjective assumptions and forecasts for the future, and estimates are inherently subject to risks and uncertainties.

To investigate the clinicopathologic characteristics and the prognostic impact of PIK3CA gene amplification in curatively resected esophageal squamous cell carcinoma (ESCC). Using 534 curatively resected ESCCs, the PIK3CA gene copy number was evaluated with fluorescent in situ hybridization. PIK3CA amplification was defined as PIK3CA/centromere 3 ratio is ≥ 2.0 or average number of PIK3CA signals/tumor cell nucleus ≥ 5.0. PIK3CA mutations in exon 9 and 20, encoding the highly conserved helical and kinase domains were assessed by direct sequencing in 388 cases. PIK3CA amplification was detected in 56 (10.5%) cases. PIK3CA amplification was significantly associated with higher T-stage (P=0.026) and pathologic stage (P=0.053). PIK3CA amplification showed a significantly shorter disease free survival (DFS) compared with that of non-amplified group (33.4 vs 63.1 months, P=0.019). After adjusting for gender, tumor location, pathologic stage, histologic grade and adjuvant treatment, PIK3CA amplification was significantly associated with a shorter DFS (adjusted hazard ratio [AHR] 1.53; 95% CI, 1.10-2.17; P=0.02). Though the statistical insignificance, PIK3CA amplification showed tendency of shorter OS (52.1 vs 96.5 moths, P=0.116). PIK3CA mutations were detected in 6 (1.5%) of 388 cases; 5 cases with exon 9 mutations in E545K while one exon 20 mutation in H1047L. PIK3CA amplification is a frequent oncogenic alteration and associated with shorter survival, suggesting its role as a prognostic biomarker in resected ESCC. PIK3CA amplification may represent a promising therapeutic target for ESCC.

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