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Mestrado Bolonha em Finanças This Equity Research in the Food and Retail Industry follows the research report format recommended by the CFA Institute. The company under analysis is Tesco PLC and the main goal is to provide an estimation of the company’s PT for the end of 2021, considering the close share price on 30th June 2021. Events that may have happened after this date were not considered for the valuation. Tesco PLC is the largest food retailer in the UK and one of the most valuable grocery companies worldwide. The company is listed at the London Stock Exchange, and it is part of the FTSE 100 index. Nowadays Tesco has its stores spread across the UK, Republic of Ireland and in Central Europe, offering a wide range of products. This project provides an overview of the company including its history, business model, strategy, key performance indicators and the company’s corporate governance. Additionally, because Tesco was the first UK retailer to issue an 8.5-year Sustainability Linked Bonds (SLB) of £750m, it was considered important to create an ESG topic as it is incorporated in the company’s strategy. Indicators like GDP growth, unemployment rate, inflation, population growth and levels of disposable income were analyzed on the Economic Outlook topic. The highlight of these macroeconomic indicators was because they directly influence the performance of the food retail industry, both supply and demand, each one in their own way. Moreover, the analysis provides information about Competitive Positioning including SWOT and PESTEL, as well as the identification of Tesco peers’ companies using the SARD approach. After understanding the company’s business and projecting all FS, the valuation was conducted applying two approaches: the Absolute Valuation Approach using DCF, APV and DDM method; and Relative Valuation Approach through multiples of the peer group. To evaluate the risks of the company and support the final recommendation, a risk matrix was firstly performed, followed by a sensitivity analysis of the critical variables (kd, rf, MRP and growth) through Monte Carlo Simulation. Based on PT of 282.86 GBX/share, 2021YE, using the DCF method, an upside potential of 26.87% was reached, against the closing price of 222.95 GBX/share. A medium risk was considered based on: Brexit, a slowdown of the overall macroeconomic indicators and the highly competitive pressure and mature market. Esta avaliação de empresa sobre a Indústria de retalho alimentar segue o formato recomendado pelo CFA Instititute. A empresa em análise é a Tesco PLC e o principal objetivo é fornecer uma estimativa do preço alvo (PT) da empresa para o final de 2021, considerando a cotação de fecho de 30 de junho de 2021. Quaisquer eventos que possam ocorrer após essa data não foram considerados na avaliação. Tesco PLC é o maior retalhista alimentar do Reino Unido e uma das mais valiosas empresas neste segmento no mundo. A empresa está cotada na Bolsa de Valores de Londres e faz parte do índice FTSE 100. Hoje em dia a Tesco tem as suas lojas espalhadas pelo Reino Unido, Irlanda e Europa Central, oferecendo uma vasta gama de produtos. Este projeto fornece uma visão geral da empresa incluindo a sua história, modelo de negócio e estratégia, indicadores-chave de desempenho e modelo corporativo. Além disso, como a Tesco foi pioneira na indústria do retalho alimentar, no RU, a emitir títulos vinculados à sustentabilidade, de 8.5 anos de £750 milhões, foi considerado importante criar um tópico de ESG, uma vez que está incorporado na estratégia da empresa. Indicadores como o crescimento do PIB, inflação, taxa de desemprego, crescimento populacional e níveis de rendimento disponíveis foram analisados no tópico “Economic Outlook”. O destaque destes indicadores macroeconómicos deve-se ao facto de estes influenciarem diretamente o desempenho da indústria, tanto a nível da oferta como da procura. Além disso, a análise fornece informações sobre o posicionamento competitivo da empresa, incluindo as análises SWOT e PESTEL, bem como a identificação de empresas semelhantes à Tesco, através da abordagem SARD. Depois de compreender melhor o negócio da empresa e projetar todas as Demonstrações Financeiras, a avaliação foi conduzida aplicando duas abordagens: Avaliação Absoluta usando os métodos dos Fluxos de Caixa atualizados (DCF), Valor Atual Ajustado (APV) e o modelo de atualização dos dividendos (DDM); e uma Avaliação Relativa por meio de múltiplos do grupo de empresas mencionado anteriormente. Para avaliar os riscos da empresa e dar suporte a recomendação final, foi realizada uma matriz de risco, seguida de uma análise de sensibilidade às variáveis consideradas mais críticas (custo da dívida, taxa livre de risco, risco de mercado e taxa de crescimento futura) através da Simulação de Monte Carlo. Com base no PT de 282.86 GBX/ação obtido através do método DCF, foi alcançada uma potencial valorização de 26.87% comparativamente com o preço de fecho de 222.95 GBX/ação. Foi considerado um investimento de risco médio tendo em conta os seguintes fatores: Brexit, desaceleração dos fatores macroeconómicos e alta pressão competitiva num mercado maduro. info:eu-repo/semantics/publishedVersion

Overcoming the highly immunosuppressive glioblastoma (GBM) microenvironment is critical to successful immunotherapy. In a recently-launched phase I trial we are examining the safety and feasibility of a novel adoptive cell immunotherapy platform, activated T cells (ATC) with anti-CD3 X anti-EGFR bispecific antibody (EGFR BATs), for patients with newly-diagnosed GBM. Autologous T cells obtained before radiation and chemotherapy are expanded and activated, becoming cytotoxic T lymphocytes. We postulate that these activated T cells armed with bispecific antibody will enhance the response to radiation/temozolomide and potentially increase trafficking to the GBM microenvironment. In a 3 + 3 design dose-escalation trial, we will determine the maximum tolerated dose (MTD) of three dose tiers of EGFR BATs (80, 120 and 160 billion cells divided in eight infusions) in combination with radiation/temozolomide in patients with newly-diagnosed GBM. Patients undergo leukapheresis prior to initiating radiation/temozolomide. Patients receive EGFR BATs on days 14 and 21 after finishing concurrent RT/ temozolomide and on day 21 of six cycles of adjuvant temozolomide. We are measuring peripheral blood immune response before and after immunotherapy and correlating the results with patient characteristics and clinical outcomes. The first four patients have been treated at the first dose tier (80 billion cells) without any dose-limiting toxicity. Updated safety and feasibility results on the patients in the first two dose tiers will be presented, as well as immune monitoring studies, imaging studies, and clinical outcomes.

BACKGROUND AND PURPOSE: Diffuse lower-grade gliomas are classified into prognostically meaningful molecular subtypes. We aimed to determine the impact of surgical resection on overall survival in lower-grade glioma molecular subtypes. MATERIALS AND METHODS: For 172 patients with lower-grade gliomas (World Health Organization grade II or III), pre- and postsurgical glioma volumes were determined using a semiautomated segmentation software based on FLAIR or T2-weighted MR imaging sequences. The association of pre- and postsurgical glioma volume and the percentage of glioma resection with overall survival was determined for the entire cohort and separately for lower-grade glioma molecular subtypes based on isocitrate dehydrogenase (IDH) and 1p/19q status, after adjustment for age, sex, World Health Organization grade, chemotherapy administration, and radiation therapy administration. RESULTS: For the entire cohort, postsurgical glioma volume (hazard ratio, 1.80; 95% CI, 1.18–2.75; P = .006) and the percentage of resection (hazard ratio, 3.22; 95% CI, 1.79–5.82; P < .001) were associated with overall survival. For IDH-mutant 1p/19q-codeleted oligodendrogliomas, the percentage of resection (hazard ratio, 6.69; 95% CI, 1.57–28.46; P = .01) was associated with overall survival. For IDH-mutant 1p/19q-noncodeleted astrocytomas, presurgical glioma volume (hazard ratio, 3.20; 95% CI, 1.22–8.39; P = .018), postsurgical glioma volume (hazard ratio, 2.33; 95% CI, 1.32–4.12; P = .004), and percentage of resection (hazard ratio, 4.34; 95% CI, 1.74–10.81; P = .002) were associated with overall survival. For IDH-wild-type lower-grade gliomas, pre-/postsurgical glioma volume and percentage of resection were not associated with overall survival. CONCLUSIONS: The extent of surgical resection has a differential survival impact in patients with lower-grade gliomas based on their molecular subtype. IDH-mutant lower-grade gliomas benefit from a greater extent of surgical resection, with the strongest impact observed for IDH-mutant 1p/19q-noncodeleted astrocytomas.

Background Glioblastoma (GBM) is a highly aggressive malignant primary brain tumor, characterized by rapid growth, diffuse infiltration of cells into both adjacent and remote brain regions, and a generalized resistance to currently available treatment modalities. Recent reports in the literature suggest that Signal Transducers and Activators of Transcription (STATs) play important roles in the regulation of GBM pathophysiology. Methods STAT6 protein expression was analyzed by Western blotting in GBM cell lines and by immunohistochemistry in a tissue microarray (TMA) of glioma patient tissues. We utilized shRNA against STAT6 to investigate the effects of prolonged STAT6 depletion on the growth and invasion of two STAT6-positive GBM cell lines. Cell proliferation was assessed by measuring 3H-Thymidine uptake over time. Invasion was measured using an in vitro transwell assay in which cells invade through a type IV collagen matrix toward a chemoattractant (Fetal Bovine Serum). Cells were then stained and counted. Kaplan-Meyer survival curves were generated to show the correlation between STAT6 gene expression and patient survival in 343 glioma patients and in a subset of patients with only GBM. Gene expression microarray and clinical data were acquired from the Rembrandt 1 public data depository (https://caintegrator.nci.nih.gov/rembrandt/). Lastly, a genome-wide expression microarray analysis was performed to compare gene expression in wild-type GBM cells to expression in stable STAT6 knockdown clones. Results STAT6 was expressed in 2 GBM cell lines, U-1242MG and U-87MG, and in normal astrocytes (NHA) but not in the U-251MG GBM cell line. In our TMA study, STAT6 immunostaining was visible in the majority of astrocytomas of all grades (I-IV) but not in normal brain tissue. In positive cells, STAT6 was localized exclusively in the nuclei over 95% of the time. STAT6-deficient GBM cells showed a reduction in 3H-Thymidine uptake compared to the wild-type. There was some variation among the different shRNA- silenced clones, but all had a reduction in 3H-Thymidine uptake ranging from 35%- 70% in U-1242MG and 40- 50% in U-87MG cells. Additionally, STAT6- depleted cells were less invasive than controls in our in vitro transmembrane invasion assay. Invasiveness was decreased by 25-40% and 30-75% in U-1242MG and U-87MG cells, respectively. The microarray analysis identified matrix metalloproteinase 1 (MMP-1) and urokinase Plasminogen activator (uPA) as potential STA6 target genes involved in the promotion of GBM cell invasion. In a Kaplan-Meier survival curve based on Rembrandt 1 gene expression microarray and clinical data, there was a significant difference in survival (P < 0.05) between glioma patients with up- and down-regulated STAT6. Decreased STAT6 expression correlated with longer survival times. In two subsets of patients with either grade IV tumors (GBM) or Grade II/III astrocytomas, there was a similar trend that however did not reach statistical significance. Conclusions Taken together, these findings suggest a role for STAT6 in enhancing cell proliferation and invasion in GBM, which may explain why up-regulation of STAT6 correlates with shorter survival times in glioma patients. This report thus identifies STAT6 as a new and potentially promising therapeutic target.