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."

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 they have hosted an Investor and Analyst meeting in New York and presented clinical and corporate updates that included progress with pipeline development and manufacturing process optimization (Press release, Adaptimmune, APR 22, 2016, View Source;p=RssLanding&cat=news&id=2159734 [SID:1234511272]).

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"At today’s event, we were delighted to present an overview of our T-cell therapy and Adaptimmune’s position within the exciting immune-oncology field," said James Noble, Chief Executive Officer. "We also reported on our upcoming goals and took the opportunity to announce MAGE-A4 as the company’s next target with the objective of achieving IND acceptance in 2017."

The presentations included updates on the company’s synovial sarcoma and multiple myeloma studies, as well as on progress with optimization of manufacturing processes and the construction of a dedicated manufacturing plant in Philadelphia scheduled to open in 2017.

Adaptimmune also announced the establishment of its scientific advisory board, to be chaired by cancer immunotherapy expert, Crystal Mackall, M.D., Professor of Pediatrics and Medicine and Associate Director of the Stanford Cancer Institute, and the adoption of the name SPEAR T-cells (Specific Peptide Enhanced Affinity Receptor T-cells) to describe its proprietary technology.

In addition to James Noble, CEO, the presenters were:

Helen Tayton-Martin Ph.D., MBA, Chief Operating Officer, Adaptimmune
Bent Jakobsen, Ph.D., Scientific Founder, Adaptimmune
Stephan Grupp, M.D., Ph.D, Novotny Professor of Pediatrics, University of Pennsylvania Perelman School of Medicine
Aaron Rapoport, M.D., Professor of Medicine, Gary Jobson Professor in Medical Oncology, University of Maryland Marlene and Stewart Greenebaum Cancer Center
Rafael Amado, M.D., Chief Medical Officer, Adaptimmune
Gwendolyn Binder-Scholl, Ph.D., Chief Technology Officer, Adaptimmune
A summary of clinical and corporate highlights presented at the Investor and Analyst Day is set out below. The slide presentation and a replay of the webcast from the event will be available on the company’s website for 30 days following the event at ir.adaptimmune.com.

Clinical and corporate highlights through April 2016:

Proprietary SPEAR T-cell technology that uniquely delivers:
Correctly identified targets
Specificity and optimal affinity TCRs
‘Supra-natural’ TCRs to accelerate programs
Enhanced effectiveness of TCRs: Generation 2 and 3
Multiple clinical responses in synovial sarcoma, a solid tumor
New images presented showing resolution of large solid lesions
Cohort 2 suggests responses in low expressers
Cohort 3 suggests importance of fludarabine
Cohort 4 starting shortly

Over 90% response rate in multiple myeloma study in conjunction with ASCT
Median overall survival of ~3 years (as of January 2016)
Pivotal studies in sarcoma to start in 4Q16/1Q17
Company INDs open for NY-ESO, MAGE-A10 and AFP
Next IND in 2017: MAGE-A4
Generation 2 INDs from 2017

These TCRs all derive from Adaptimmune’s proprietary technology
Active programs give broad coverage of tumors

Milestones met through April 2016
Expanded into autoimmune
Expanded strategic immunotherapy collaboration with GSK
Secured NY-ESO breakthrough therapy designation in synovial sarcoma
Secured NY-ESO orphan drug designation
IND opened for AFP in hepatocellular cancer

Manufacturing processes optimized
Proprietary T-cell expansion method
Commercial-ready process in place
EU and US contract manufacturers in place

Progressed construction of a dedicated manufacturing plant in Philadelphia
Manufacturing plant scheduled to open in 2017
Potential to enable treatment of up to 1,200 patients per year

Financial position confirmed
Total liquidity position of $248 million as of December 31, 2015
Current capital can fund the business through mid-2018

Cathepsin S has been implicated in a variety of malignancies with genetic ablation studies demonstrating a key role in tumor invasion and neo-angiogenesis. Thus, the application of cathepsin S inhibitors may have clinical utility in the treatment of cancer. In this investigation, we applied a cell-permeable dipeptidyl nitrile inhibitor of cathepsin S, originally developed to target cathepsin S in inflammatory diseases, in both in vitro and in vivo tumor models.
Validation of cathepsin S selectivity was carried out by assaying fluorogenic substrate turnover using recombinant cathepsin protease. Complete kinetic analysis was carried out and true K i values calculated. Abrogation of tumour invasion using murine MC38 and human MCF7 cell lines were carried out in vitro using a transwell migration assay. Effect on endothelial tube formation was evaluated using primary HUVEC cells. The effect of inhibitor in vivo on MC38 and MCF7 tumor progression was evaluated using cells propagated in C57BL/6 and BALB/c mice respectively. Subsequent immunohistochemical staining of proliferation (Ki67) and apoptosis (TUNEL) was carried out on MCF7 tumors.
We confirmed that this inhibitor was able to selectively target cathepsin S over family members K, V, L and B. The inhibitor also significantly reduced MC38 and MCF7 cell invasion and furthermore, significantly reduced HUVEC endothelial tubule formation in vitro. In vivo analysis revealed that the compound could significantly reduce tumor volume in murine MC38 syngeneic and MCF7 xenograft models. Immunohistochemical analysis of MCF7 tumors revealed cathepsin S inhibitor treatment significantly reduced proliferation and increased apoptosis.
In summary, these results highlight the characterisation of this nitrile cathepsin S inhibitor using in vitro and in vivo tumor models, presenting a compound which may be used to further dissect the role of cathepsin S in cancer progression and may hold therapeutic potential.

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This multicentre, open-label, randomized, controlled phase II study evaluated cilengitide in combination with cetuximab and platinum-based chemotherapy, compared with cetuximab and chemotherapy alone, as first-line treatment of patients with advanced non-small-cell lung cancer (NSCLC).
Patients were randomized 1:1:1 to receive cetuximab plus platinum-based chemotherapy alone (control), or combined with cilengitide 2000 mg 1×/week i.v. (CIL-once) or 2×/week i.v. (CIL-twice). A protocol amendment limited enrolment to patients with epidermal growth factor receptor (EGFR) histoscore ≥200 and closed the CIL-twice arm for practical feasibility issues. Primary end point was progression-free survival (PFS; independent read); secondary end points included overall survival (OS), safety, and biomarker analyses. A comparison between the CIL-once and control arms is reported, both for the total cohorts, as well as for patients with EGFR histoscore ≥200.
There were 85 patients in the CIL-once group and 84 in the control group. The PFS (independent read) was 6.2 versus 5.0 months for CIL-once versus control [hazard ratio (HR) 0.72; P = 0.085]; for patients with EGFR histoscore ≥200, PFS was 6.8 versus 5.6 months, respectively (HR 0.57; P = 0.0446). Median OS was 13.6 for CIL-once versus 9.7 months for control (HR 0.81; P = 0.265). In patients with EGFR ≥200, OS was 13.2 versus 11.8 months, respectively (HR 0.95; P = 0.855). No major differences in adverse events between CIL-once and control were reported; nausea (59% versus 56%, respectively) and neutropenia (54% versus 46%, respectively) were the most frequent. There was no increased incidence of thromboembolic events or haemorrhage in cilengitide-treated patients. αvβ3 and αvβ5 expression was neither a predictive nor a prognostic indicator.
The addition of cilengitide to cetuximab/chemotherapy indicated potential clinical activity, with a trend for PFS difference in the independent-read analysis. However, the observed inconsistencies across end points suggest additional investigations are required to substantiate a potential role of other integrin inhibitors in NSCLC treatment.
NCT00842712.
© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].

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This quadrivalent human papillomavirus (qHPV) (HPV6, -11, -16, and -18) vaccine long-term follow-up (LTFU) study is an ongoing extension of a pivotal clinical study (FUTURE II) taking place in the Nordic region. The LTFU study was designed to evaluate the effectiveness, immunogenicity, and safety of the qHPV vaccine (Gardasil) for at least 10 years following completion of the base study. The current report presents immunogenicity data from testing samples of the year 5 LTFU visit (approximately 9 years after vaccination). FUTURE II vaccination arm subjects, who consented to being followed in the LTFU, donated serum at regular intervals and in 2012. Anti-HPV6, -11, -16, and -18 antibodies were detected by the competitive Luminex immunoassay (cLIA), and in addition, serum samples from 2012 were analyzed by the total IgG Luminex immunoassay (LIA) (n = 1,598). cLIA geometric mean titers (GMTs) remained between 70% and 93% of their month 48 value depending on HPV type. For all HPV types, the lower bound of the 95% confidence interval (CI) for the year 9 GMTs remained above the serostatus cutoff value. The proportion of subjects who remained seropositive based on the IgG LIA was higher than the proportion based on cLIA, especially for anti-HPV18. As expected, the anti-HPV serum IgG and cLIA responses were strongly correlated for all HPV types. Anti-HPV GMTs and the proportion of vaccinated individuals who are seropositive remain high for up to 9 years of follow-up after vaccination.
Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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