Protection of Whistleblowers by the European Union, the Council of Europe, and the European Court of Human Rights

Whistleblower protection in the European Union is undergoing significant developments. The new Directive (EU) 2019/1937 of the European Parliament and of the Council of 23 October 2019 on the protection of persons reporting breaches of Union law sets a minimum standard for the protection of whistleblowers. It is awaiting implementation in Member States' national law by December 2021. However, a certain level of protection is also guaranteed by the European Court of Human Rights case law principles. Reports of illegal activities provided from close internal sources can strengthen the protection of the EU's financial interests. Adequate protection is needed to prevent retaliation against whistleblowers. As the deadline for transposing this directive approaches, the article aims to analyse the Directive 2019/1973 and compare it with the protection guaranteed by Article 10 of the European Convention on Human Rights.

Implementation of the EPPO Regulation from the Slovak Perspective

Nowadays, 22 Member States are participating in enhanced cooperation for establishment of the European Public Prosecutor's Office. Due to the fact that the establishment and exercise of powers of the European Public Prosecutor's Office significantly changes the current concept of EU criminal law, it was necessary for the participating Member States to adapt to this change. To ensure effective application of the Regulation in practice, the Member States had to adopt different implementing measures. As in other Member States, also the national authorities of the Slovak Republic needed to consider necessary legislative measures ensuring effective application of the EPPO Regulation for the purpose of investigating and prosecuting criminal offences affecting financial interests of the EU.

Analysis of theoretical and methodological approaches to determining the concept of "customs regimes"

The article analyzes the concept of "customs regime", characteristic features are formulated, main elements, goals and functions of customs regimes in the development of foreign economic relations. The classical classification of customs regimes under the Customs Code of Ukraine is substantiated. Based on the analysis, a position on the study concept is substantiated, the interpretation of the category "Customs regimes" is provided. The conducted research confirms that under the customs regime, we understand the set of customs procedures that establish the rules for moving goods through the customs border of Ukraine and their further use in order to ensure the interests of the state in the customs sphere. The functions of customs regimes are analyzed: fiscal, which finds its implementation in the collection of customs payments in order to ensure the financial interests of the state in foreign economic activity; stimulating, implemented by exempt from customs taxation and the use of non-tariff regulation, simplification of customs procedures in order to stimulate subjects of foreign economic activity, promoting the development of a national economy, etc.; protective, which involves the use of non-tariff regulatory measures and aims to protect the economic and other national interests of the state by introducing a licensing, quota and other non-tariff restrictions when placing goods in customs regimes; control - aimed at ensuring compliance with the norms of the current legislation of Ukraine in the customs sphere, which is implemented through specific methods and forms inherent in control in the field of public administration; the regulatory, purpose of which is to regulate the order of action when placing the goods in the customs regime associated with the direction of movement of goods through the customs border, the definition of the status of goods and operations with it, etc. According to the results of generalization, the study is substantiated by the classification of customs regimes, which includes: a) the main (import (issue for free circulation) and export) as customs regimes aimed at ensuring the state's financial interests in foreign economic activity; protection of its economic and other national interests; b) preferential customs regimes (transit, customs warehouse, free customs zone, temporary import of goods to customs territory and exports at its boundaries, processing in customs territory and abroad), the purpose of applying which is to stimulate the subjects of foreign economic activity of the state, development of the national industry, promoting international trade, economic relations and relationships in the humanitarian sphere; c) special customs regimes (Repimport, re-export, duty-free trade, destruction or destruction and refusal of the state) that are not provided for by the European Union's customs law and in its essence or are auxiliary, or such that define certain signs of goods.

ENTERPRISE’S FINANCIAL SECURITY IN THE CONTEXT OF SUSTAINABLE DEVELOPMENT

The financial system of Ukraine as a country with a small open economy is especially affected by global turbulence. A significant imbalance of global financial resources, their significant gap from the real sector of the economy leads to the formation of permanent financial crises, which gives rise to internal instability of the financial sector of the economy, lack of confidence in the banking system and a decrease in demand for final products, which entails a decrease in the level of financial security of enterprises. In such conditions, ensuring the financial security of enterprises becomes important not only for the formation of financial security of the state, but also for protecting the financial interests of their owners, and other stakeholders – managers, employees, counterparties, banks and other financial institutions.

Debt and International Organizations

International financial organizations that lend to developing countries are the subject of controversy. Their functions, structures and effectiveness have generated important debates across disciplines, analysts and positions on the ideological-political spectrum. What interests and logic motivate the international financial institutions’ (IFIs) loans? Following an international political economy perspective and mainly based on the literature produced in the early 21st century, we analyze the role played by three variables: the geopolitical and financial interests of powerful global actors, institutional and bureaucratic logic, and the borrower’s interest and domestic policy. These three variables interact and influence the financial decisions made by the International Monetary Fund (IMF), the World Bank, and the major regional development banks (the Inter-American Development Bank [IADB], Asian Development Bank [AsDB], and African Development Bank [AfDB]). On the other hand, what are the main economic and political effects in the recipient countries? The IMF’s credit tackles balance-of-payments crises mainly through adjusting domestic output and consumption, which usually has negative social costs. Development bank lending has diverse effects. Although it tends to boost growth and strengthen domestic accountability, it does not always guarantee the attainment of development goals. In this sense, the literature has found negative impacts on labor rights and forestry, while improvements in health and education cannot always be sustained in the long run.

Pragmatic structure of bargaining in Hindi: An (im)politeness and banter-based exposition

Bargaining is an accepted and commonplace practice in fixing the rate of virtually any kind of item purchased in India. Taking excerpts from a corpus of Eastern Hindi, in this paper, I have explored the linguistic behaviour of Eastern Hindi speakers in bargaining context in terms of the theory of banter and discuss how it actually serves to negotiate the competing motivations of protecting ones financial interests in a bargain as well as establishing and maintaining long-term positive inter-personal relationship with each other. As in conventional banter, in bargaining also, potentially impolite linguistic behaviour is used to show the in-group identity and establish a positive inter-personal relationship. I shall further argue that a bargain interaction involves both the conventional and impoliteness mitigation banter as well as conventional (im)politeness. In general, a successful bargain depends on what kind of linguistic behaviour is employed in which phase. The study shows that conventional politeness in initiation phase, conventional solidarity banter in argumentation phase and impoliteness mitigation banter or even non-polite behaviour in settlement phase is employed in successful bargains.

DEVELOPMENT OF THE FINANCIAL SECURITY SYSTEM OF THE BANKING

This study determines the preconditions and significance of the development of the system of financial security of the banking sector (FSBS) of the national economy, reveals gaps in modern coverage of this issue and highlights the approaches to the development of the system of FSBS provision. The author has critically analyzed the views of researchers on the provision of FSBS described in the economic literature and theses on this issue. It has been discovered that the issues of definition of the specific objects of banking security remains unsolved; providing FSBS is sometimes limited by the development and implementation of its strategy, which does not take into account the whole set of close ties of different economic agents, their various entities and government agencies, sectors of the national economy, as well as existing differences in their economic / financial interests; the destructive influence of the endogenous environment of the banking sector is not taken into account. According to the author’s definition, presented in the article, the system of FSBS provision is an organic combination of security subsystems that are continuously developing on a stable planned basis by the system entities to achieve its goals, perform tasks of a conceptual / strategic nature according to object-oriented approach to FSBS provision; a set of optimally alternative and coordinated preventive, current and corrective measures. Based on the study it has been defined what determines the effectiveness of such a system. It has been also determined that the development and further functioning of the system of FSBS provision should be based on the relevant concept, strategy, policy, priorities and current measures, reasonable definition of goals and objectives of such system, its subject, objects and subjects, principles of development and functioning, mechanisms, methods and tools for providing FSBS, determining reserves to increase its level as well as high-quality security support subsystems of the system of FSBS provision. The author’s vision of the components of the development of system of FSBS provision is described. Keywords: financial security, financial security system of the banking sector, principles of development of the financial security system of the banking sector, purpose, objective, object, subject, banking sector JEL Classification G21 Formulas: 0; fig.: 1; tabl.: 0; bibl.: 12.

Multicenter, Open-Label, Phase 3 Study of Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Recipients with Epstein-Barr Virus-Driven Post Transplant Lymphoproliferative Disease after Failure of Rituximab or Rituximab and Chemotherapy (ALLELE)

Background: Tabelecleucel is an investigational, off-the-shelf, allogeneic Epstein-Barr virus (EBV)-specific T-cell immunotherapy being studied in patients (pts) with serious EBV-driven diseases, including post-transplant lymphoproliferative disease (EBV + PTLD). The median overall survival (OS) after treatment failure of rituximab is short at ~1.7 months in EBV + PTLD following hematopoietic cell transplant (HCT) (Socié EBMT 2020) and ~3 months in solid organ transplant (SOT) recipients with EBV + PTLD whose disease relapsed after rituximab and who did not respond to or did not receive chemotherapy (CT) (Zimmerman EHA 2019). These poor outcomes demonstrate an urgent unmet need for effective therapies in this ultra-rare serious disease. Promising outcomes have previously been demonstrated (Prockop JCI 2020). Additionally, we have shown clinical benefit with a >60% objective response rate (ORR) and >80% estimated 2-year OS rates (Prockop EBMT 2021, Prockop ATC 2021) in pts with EBV + PTLD, irrespective of pts achieving a complete response (CR) or partial response (PR) to tabelecleucel. Safety data have been assessed in >150 pts with EBV + PTLD treated with tabelecleucel with tumor flare reaction (TFR) as the only identified risk. Here, for the first time, we report interim efficacy and safety results from the pivotal phase 3 clinical trial ALLELE (NCT03394365) - a multicenter, open-label study of tabelecleucel after failure of rituximab ± CT in pts with EBV + PTLD following SOT or HCT. Methods: ALLELE is evaluating the clinical benefit of tabelecleucel in two cohorts: (1) pts with EBV + PTLD following SOT after failure of rituximab ± CT (n=33), and (2) pts with EBV + PTLD following HCT after failure of rituximab monotherapy (n=33). Tabelecleucel is administered at a dose of 2 x 10 6 cells/kg on days 1, 8, and 15, followed by observation through each cycle lasting 35 days. Response per clinical and radiographic assessment (by PET/CT) is evaluated by the investigator and by independent review using Lugano Classification with LYRIC modification. Key efficacy endpoints include ORR, duration of response (DOR), time to response (TTR), and OS. After treatment is completed or discontinued, pts are assessed every 3 months up to 24 months, and every 6 months thereafter for survival status up to 5 years. Results: As of May 2021, 38 pts (24 SOT, 14 HCT) were evaluable for response assessment by independent oncologic response adjudication (IORA) and had the opportunity for 6 months follow-up (Table 1). SOT and HCT pts received a median (range) of 2.0 (1-6) and 3.0 (1-5) cycles of tabelecleucel, respectively. ORR was 50% (19/38, 95% CI: 33.4, 66.6) in the overall population, 50.0% (12/24, 95% CI: 29.1, 70.9) in SOT, and 50.0% (7/14, 95% CI: 23.0, 77.0) in HCT, with a best overall response of CR (n=5, SOT; n=5, HCT) or PR (n=7, SOT; n=2, HCT; Table 2). Overall, median TTR was 1.1 months (0.7-4.7), 11 of 19 responders had a DOR lasting >6 months, and median DOR was not reached (Table 2). Median OS was 18.4 (95% CI: 6.9, NE) months overall, 16.4 (95% CI: 3.5, NE) months for SOT, and not yet reached for HCT. 1-year survival rate was 61.1% (95% CI: 42.9, 75.0) overall, 57.4% (95% CI: 35.2, 74.5) for SOT, and 66.8% (95% CI: 32.4, 86.6) for HCT. Those who responded had a longer survival compared to the non-responders, with a median OS of NE (95% CI: 16.4, NE) and 1-year survival rate of 89.2% (95% CI: 63.1, 97.2). Non-responders had a median OS of 5.7 (95% CI: 1.8, 12.1) months and 1-year survival rate of 32.4% (95% CI: 12.1, 54.9) (Table 3). Serious treatment emergent AEs (TEAEs) were reported in 62.5% of SOT and 57.1% of HCT pts. Fatal TEAEs were reported in 16.7% of SOT and 7.1% of HCT pts; none of the fatal TEAEs were related to study treatment. Tabelecleucel was well-tolerated with no reports of TFR and no confirmed evidence for graft vs host disease, organ rejection, infusion reactions, or cytokine release syndrome in relation to tabelecleucel in these treatment refractory and immunocompromised pts. Conclusions: Tabelecleucel phase 3 interim data are reported here for the first time and show clinically meaningful outcomes and promising ORR and OS in a pt population with no approved treatment options and otherwise poor survival. Tabelecleucel, an allogeneic cell therapy, was well tolerated without evidence of safety concerns typically observed with autologous chimeric antigen receptor cell therapies. Figure 1 Figure 1. Disclosures Prockop: Memorial Sloan Kettering Cancer Center: Other: S Prockop receives support for the conduct of sponsored clinical trials through MSK from Atara Biotherapeutics, Jasper and AlloVir. , Patents & Royalties: S Prockop is a co-inventor on intellectual property (IP) licensed to Atara. S Prockop has waived rights to this IP to MSK and has no personal financial interests in Atara. MSK has financial interests in Atara and IP interests relevant to this abstract. ; Atara Biotherapeutics: Other: support for the conduct of sponsored trials and Inventor; Jasper: Other: support for the conduct of sponsored trials; AlloVir: Other: support for the conduct of sponsored trials; Neovii: Consultancy; ADMA Biologics: Consultancy; MSK: Other: Inventor. Mahadeo: Atara Biotherapeutics: Consultancy. Beitinjaneh: Kite/Gilead: Other: Ad Board Event Attendee. Choquet: Sanofi, Celegene, Roche, Abbvie, Sandoz, Janssen, Takeda: Consultancy. Stiff: Cellectar: Research Funding; CRISPR: Consultancy; Gamida-Cell, Atara, Amgen, Incyte, Takeda, Macrogenetics, Eisai: Research Funding. Reshef: Bayer, BMS, Regeneron, TScan, Synthekine, Atara, Jasper: Consultancy. Dahiya: Kite, a Gilead Company: Consultancy; Miltenyi Biotech: Research Funding; Atara Biotherapeutics: Consultancy; Jazz Pharmaceuticals: Research Funding; BMS: Consultancy. Parmar: Atara Biotherapeutics: Current Employment. Ye: Atara Biotherapeutics: Current Employment. Gamelin: Atara Biotherapeutics: Current Employment. Dinavahi: Atara Biotherapeutics: Current Employment.

Interim Results of a Pilot, Prospective, Randomized, Double-Blinded, Vehicle- and Comparator-Controlled Trial on Safety and Efficacy of a Topical Inhibitor of Janus Kinase 1/2 (Ruxolitinib INCB018424 Phosphate 1.5% Cream) for Non-Sclerotic and Superficially Sclerotic Chronic Cutaneous Graft-Versus-Host Disease

Oral ruxolitinib has been successfully used for the treatment of acute and chronic graft-versus-host disease (cGvHD) and topical ruxolitinib has demonstrated efficacy in clinical trials for vitiligo, atopic dermatitis, and psoriasis. Background: There are no FDA-approved topical treatments for cutaneous cGvHD. Topical corticosteroids are the mainstay of skin-directed therapy for the inflammatory-phase cutaneous cGvHD but are associated with significant side effects such as skin thinning, bruising, striae, infections, and acne, and may incompletely treat cutaneous cGvHD, prompting use of systemic therapies. Methods. We conducted a prospective, randomized, double-blind, vehicle- and comparator-controlled, phase 2, proof-of-concept trial evaluating the efficacy and safety of topical ruxolitinib 1.5% cream in patients 12 years of age or older with cutaneous nonsclerotic (lichen-planus like, poikilodermatous) and superficially sclerotic (lichen sclerosus, morphea-like) cGvHD with ≥2% of body surface area (BSA) affected at a single, academic transplantation center in the United States. Patients were only eligible to enroll if systemic therapy, when applicable, was stable for ≥ 4 weeks and concurrent topical therapy (including phototherapy) was not used. Patients were randomly assigned (1:1) to receive topical ruxolitinib 1.5% cream left side of face/body or right side of face/body with placebo vehicle cream to contralateral side of face/body twice daily to for 28 days, followed by an optional open label extension to both sides of 28 days for interested patients. The primary end point was efficacy as measured by BSA of the GvHD rash on the side of face/body treated with topical ruxolitinib cream vs contralateral side treated with vehicle at Day 28. Secondary endpoints were Physician's Global Assessment of clinical condition (PGA) and Composite Assessment of Index Lesion Severity (CAILS) of the ruxolitinib-treated side vs vehicle-treated side at Day 14 and 28. Interim analyses were performed once 10 patients were evaluable of the planned 24 patients. Results. Between 6/28/19 and 5/14/21, a total of 13 patients (mean age 52.6 years [SD 20.0]; 7 [54%] female and 6 [46%] male) underwent randomization; 11 patients completed Day 14 assessments, 12 patients Day 28 assessments, and 10 patients Day 56 assessments. Patients had a history of acute leukemia (N=8 [62%]), non-Hodgkin lymphoma (N=3 [23%]), myeloproliferative neoplasm (N=1 [8%]), or aplastic anemia (N=1 [8%]). Median time from transplant to enrollment was 665 days (IQR 433-1355), and from cGvHD onset to enrollment 283 days (IQR 115-867). Chronic GvHD was NIH mild (8%), moderate (23%), or severe (62%), predominantly classic (85% vs. overlap 15%), with 46% having 4 or more involved organs. Most patients were enrolled for treatment of cutaneous nonsclerotic cGvHD (N=10, 77%) with lichen planus-like (N=8), papulosquamous (N=1), and maculopapular rash/erythema features (N=1). Three patients were enrolled for treatment of lichen sclerosus-like cGvHD. Patients were heavily pretreated with 4 (31%) having 3 or more prior lines of systemic therapy for cGvHD. Most patients had failed at least 2 topical therapies, with 77% previously failed topical steroids, 24% topical calcineurin inhibitors, and 24% phototherapy. There was a trend in reduced BSA of cGvHD on the treatment side compared to the vehicle side from Day 1 (13.4 on treatment/vehicle) to Day 14 (10.9 vs 13.8; p=0.06) and continuing to Day 28 (7.7 vs 11.0; p=0.15), respectively. PGA (Day 1: 5 treatment/vehicle) of treatment side was significantly improved starting at Day 14 (3.3 treatment vs 4.4 vehicle; p=0.024), with continued improvement at Day 28 (2.5 vs 4.0; p= 0.026). CAILS (Day 1: 15.6 treatment vs 15.5 vehicle; p=0.83) of treatment side was also significantly improved starting at Day 14 (9.0 vs 13.3; p=0.02). There were no serious adverse events (SAEs) reported. One patient had a grade 1 headache which was attributed possibly to therapy. Three patients had treatment-emergent AEs (all grade 1) that were unlikely (N=1) or unrelated (N=2) to study therapy. Conclusions. Topical ruxolitinib 1.5% cream was effective in treating cutaneous nonsclerotic and superficially sclerotic GvHD as determined by PGA and CAILS. These data suggest that ruxolitinib cream might be a safe and effective treatment option for patients with cutaneous nonsclerotic and superficially sclerotic chronic GvHD. Figure 1 Figure 1. Disclosures Markova: Alira Health Ventures: Consultancy; Incyte Corporation: Research Funding; Blueprint Medicines: Consultancy; UpToDate: Patents & Royalties: Royalties for chapter on dermatologic adverse events to targeted therapies ; Amryt Pharma: Research Funding. Perales: MorphoSys: Honoraria; Omeros: Honoraria; Cidara: Honoraria; Incyte: Honoraria, Other; Equilium: Honoraria; Medigene: Honoraria; Kite/Gilead: Honoraria, Other; Karyopharm: Honoraria; Sellas Life Sciences: Honoraria; Novartis: Honoraria, Other; Nektar Therapeutics: Honoraria, Other; Servier: Honoraria; Miltenyi Biotec: Honoraria, Other; NexImmune: Honoraria; Celgene: Honoraria; Merck: Honoraria; Takeda: Honoraria; Bristol-Myers Squibb: Honoraria. Prockop: Memorial Sloan Kettering Cancer Center: Other: S Prockop receives support for the conduct of sponsored clinical trials through MSK from Atara Biotherapeutics, Jasper and AlloVir. , Patents & Royalties: S Prockop is a co-inventor on intellectual property (IP) licensed to Atara. S Prockop has waived rights to this IP to MSK and has no personal financial interests in Atara. MSK has financial interests in Atara and IP interests relevant to this abstract. ; MSK: Other: Inventor; Neovii: Consultancy; ADMA Biologics: Consultancy; Jasper: Other: support for the conduct of sponsored trials; AlloVir: Other: support for the conduct of sponsored trials; Atara Biotherapeutics: Other: support for the conduct of sponsored trials and Inventor. Ponce: Kadmon pharmaceuticals: Consultancy, Honoraria; Ceramedix: Consultancy, Honoraria; CareDx: Consultancy, Honoraria; Seres Therapeutics: Consultancy, Research Funding; Generon Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Research Funding.