Life Science Industry Research Articles

Simple rules and heuristic decision making using the quick screen tool: A JD Bioscience case study

ABSTRACT This case study examines JD Bioscience (JDB), a South Korean pharmaceutical start-up, using the quick screen framework and its scorecard tool. The underlying rationale (the “why”) is to combat the decision-making complexities involved with new assets for licensing and acquisition within the life science industry by utilizing simple rules (the “how”) via the quick screen tool (the “what”). This article aims to explore simple rules and heuristic decision making in life science opportunities. JDB’s final score of 2.87 reflects unique attributes and developmental risks around the firm, its lead asset, and its management team. The analysis supports the application of a simple rules decision-making framework for entrepreneurs, investors, and executives. This framework identifies an opportunity’s maturation stage and roadblocks the venture needs to address. The findings shed light on JDB’s trajectory and underscore the significance of employing strategic decision-making tools in navigating the complexities of the life sciences landscape.

Building capabilities for an orchestrated customer experience in the life-sciences sector: Case study of CSL Behring

Orchestrating the right content, at the right time, with the right customer, via the right channel can be a key growth driver for products in the life-sciences industry. Starting with the right marketing foundation for content, channels and service is essential, and with the right measures in place, one can advance adoption and commercial impact quickly. As this paper explains, when seeking to unlock commercial value, it is important to partner with marketing leadership to establish a roadmap that defines desired skills, competencies, process, frameworks and technologies. This paper describes CSL Behring’s endeavours to build an orchestrated customer experience for healthcare professionals and, ultimately, patients. The insights provided should be of particular benefit to marketers within the life science sector.

Synthesis and photophysical properties of symmetrical tetraaryltetranaphtho[2,3]porphyrin derivatives

The discovery of new photosensitizers with strong absorption near-infrared region, obvious fluorescence emission, and high reactive oxygen generation ability has attracted great attention as optical agents in life science and material industry. Herein a series of meso-tetraaryltetranaphtho[2,3]porphyrins (Ar 4TNPs) with different substitutions were designed and synthesized. They had strong absorptions at ∼730 nm and fluorescence emission at ∼760 nm after excitation with ∼503 nm light. All compounds possessed excellent reactive oxygen species (ROS) generation ability. The singlet oxygen generation rate of compound 10m (meso-5,10,15,20-tetra[2-(2-hydroxyethoxy)ethylbenzoate]tetrana-phthoporphyrin) is 0.1898 s−1 with a Φ△ value of 0.73, which is significantly higher than that of verteporfin. Therefore, Ar4TNPs have great potential as an effective optical material, bio-tracker, and photodynamic drug candidate.

Risk Management in Project Planning for Life Science R&D: An Integration of the NTCP Framework

AbstractAs with many industries, the early life science R&D drug discovery sector is facing growing pressure and higher demands on products in terms of cost, quality, and time‐to‐market. Additionally, the complexity of involved targets and systems, requirements for rapid, safe, and developable candidates are increasing. The drug discovery market, often regarded as rather conservative, relies more and more on advanced technologies. It is therefore a significant task for suppliers to create good solutions that meet customer requirements. The life science industry has a long tradition of using projects as the preferred method to manage these complex systems developments, such as the production of target proteins, screening of compounds, and follow‐up of hit compounds. When applying the project approach, the level of uncertainty is usually high, and the risk of those uncertainties must be managed starting in the early planning phase. Thus, this paper focuses on the issue of how to manage risks in the early project planning phase. We first review state‐of‐the‐art practices in risk management for complex systems project management and identify an important framework, Novelty‐Technology‐Cost‐Pace (NTCP), and apply it to successful risk management for early life science projects. Through an in‐depth case study in the life science industry, we demonstrate a systemic integration of the NTPC framework into project planning.

Hepatitis B virus enhancer 1 activates preS1 and preS2 promoters of integrated HBV DNA impairing HBsAg secretion

The expression of HBsAg from integrated HBV DNA limits the achievement of functional cure for chronic hepatitis B. Thus, characterising the unique expression and secretion of HBsAg derived from integrated HBV DNA is of clinical significance. A total of 563 treatment-naive patients and 62 functionally cured patients were enrolled, and HBsAg and HBcAg immunohistochemistry of their liver biopsy tissues was conducted followed by semi-quantitative analysis. Then, based on stratified analysis of HBeAg-positive and -negative patients, long-read RNA sequencing analysis, as well as an invitro HBV integration model, we explored the HBsAg secretion characteristics of integrated HBV DNA and underlying mechanisms. In contrast to the significantly lower serum HBsAg levels, no significant decrease of intrahepatic HBsAg protein was observed in HBeAg-negative patients, as compared with HBeAg-positive patients. The results of long-read RNA sequencing of liver tissues from patients with chronic HBV infection and invitro studies using integrated HBV DNA mimicking dslDNA plasmid revealed that, the lower HBsAg secretion efficiency seen in HBeAg-negative patients might be attributed to an increased proportion of preS1 mRNA derived from integrated HBV DNA instead of covalently closed circular DNA. The latter resulted in an increased L-HBsAg proportion and impaired HBsAg secretion. Enhancer 1 (EnhI) in integrated HBV DNA could retarget preS1 (SP1) and preS2 (SP2) promoters to disrupt their transcriptional activity balance. The secretion of HBsAg originating from integrated HBV DNA was impaired. Mechanistically, functional deficiency of core promoter leads to retargeting of EnhI and thus uneven activation of the SP1 over the SP2 promoter, resulting in an increase in the proportion of L-HBsAg. Integrated hepatitis B virus (HBV) DNA can serve as an important reservoir for HBV surface antigen (HBsAg) expression, and this limits the achievement of a functional cure. This study revealed that secretion efficiency is lower for HBsAg derived from integrated HBV DNA than HBsAg derived from covalently closed circular DNA, as determined by the unique sequence features of integrated HBV DNA. This study can broaden our understanding of the role of HBV integration and shed new light on antiviral strategies to facilitate a functional cure. We believe our results are of great general interest to a broad audience, including patients and patient organisations, the medical community, academia, the life science industry and the public.

Patient listening on social media for patient-focused drug development: a synthesis of considerations from patients, industry and regulators.

Patients, life science industry and regulatory authorities are united in their goal to reduce the disease burden of patients by closing remaining unmet needs. Patients have, however, not always been systematically and consistently involved in the drug development process. Recognizing this gap, regulatory bodies worldwide have initiated patient-focused drug development (PFDD) initiatives to foster a more systematic involvement of patients in the drug development process and to ensure that outcomes measured in clinical trials are truly relevant to patients and represent significant improvements to their quality of life. As a source of real-world evidence (RWE), social media has been consistently shown to capture the first-hand, spontaneous and unfiltered disease and treatment experience of patients and is acknowledged as a valid method for generating patient experience data by the Food and Drug Administration (FDA). While social media listening (SML) methods are increasingly applied to many diseases and use cases, a significant piece of uncertainty remains on how evidence derived from social media can be used in the drug development process and how it can impact regulatory decision making, including legal and ethical aspects. In this policy paper, we review the perspectives of three key stakeholder groups on the role of SML in drug development, namely patients, life science companies and regulators. We also carry out a systematic review of current practices and use cases for SML and, in particular, highlight benefits and drawbacks for the use of SML as a way to identify unmet needs of patients. While we find that the stakeholders are strongly aligned regarding the potential of social media for PFDD, we identify key areas in which regulatory guidance is needed to reduce uncertainty regarding the impact of SML as a source of patient experience data that has impact on regulatory decision making.

Increasing the Efficiency of Emulsion Crystallization in Stirred Vessels by Targeted Application of Shear and Surfactant

Emulsions containing crystalline dispersed phases hold significant importance in pharmaceutical, chemical, and life science industries. The industrial agitation and storage of these emulsions can prompt crystallization effects within the flow field, intersecting with the primary nucleation mechanisms. Notably, contact-mediated nucleation, in which subcooled droplets crystallize upon contact with a crystalline particle, and shear-induced crystallization due to droplet deformation, are both conceivable phenomena. This study delves into the crystallization processes of emulsions in a 1 L stirred vessel, integrating an ultrasonic probe to monitor droplet crystallization progression. By scrutinizing the influence of the flow field and of the emulsifiers stabilizing the droplets, our investigation unveils the direct impact of enhanced rotational speed on accelerating the crystallization rate, correlating with increased energy input. Furthermore, the concentration of emulsifiers is observed to positively affect the crystallization process. Significantly, this pioneering investigation marks the first evaluation of emulsion crystallization considering the overlapping nucleation mechanisms seen in industrial production of melt emulsions. The findings offer valuable insights for more systematic control strategies in emulsion crystallization processes, promising more efficient and sustainable industrial practices by enabling targeted application of shear and surfactants.

Higher TP53BP2 expression is associated with HBsAg loss in peginterferon-α-treated patients with chronic hepatitis B

HBsAg loss is only observed in a small proportion of patients with chronic hepatitis B (CHB) who undergo interferon treatment. Investigating the host factors crucial for functional cure of CHB can aid in identifying individuals who would benefit from peginterferon-α (Peg-IFNα) therapy. We conducted a genome-wide association study (GWAS) by enrolling 48 patients with CHB who achieved HBsAg loss after Peg-IFNαtreatment and 47 patients who didn't. In the validation stage, we included 224 patients, of whom 90 had achieved HBsAg loss, to validate the identified significant single nucleotide polymorphisms. To verify the functional involvement of the candidate genes identified, we performed a series of invitro and invivo experiments. GWAS results indicated a significant association between the rs7519753C allele and serum HBsAg loss in patients with CHB after Peg-IFNα treatment (p= 4.85× 10-8, odds ratio= 14.47). This association was also observed in two independent validation cohorts. Expression quantitative trait locus analysis revealed higher hepatic TP53BP2 expression in individuals carrying the rs7519753C allele (p= 2.90× 10-6). RNA-sequencing of liver biopsies from patients with CHB after Peg-IFNα treatment revealed that hepatic TP53BP2 levels were significantly higher in the HBsAg loss group compared to the HBsAg persistence group (p= 0.035). Invitro and invivo experiments demonstrated that loss of TP53BP2 decreased interferon-stimulated gene levels and the anti-HBV effect of IFN-α. Mechanistically, TP53BP2 was found to downregulate SOCS2, thereby facilitating JAK/STAT signaling. The rs7519753C allele is associated with elevated hepatic TP53BP2 expression and an increased probability of serum HBsAg loss post-Peg-IFNα treatment in patients with CHB. TP53BP2 enhances the response of the hepatocyte to IFN-α by suppressing SOCS2 expression. Chronic hepatitis B (CHB) remains a global public health issue. Although current antiviral therapies are more effective in halting disease progression, only a few patients achieve functional cure for hepatitis B with HBsAg loss, highlighting the urgent need for a cure for CHB. This study revealed that the rs7519753C allele, which is associated with high expression of hepatic TP53BP2, significantly increases the likelihood of serum HBsAg loss in patients with CHB undergoing Peg-IFNα treatment. This finding not only provides a promising predictor for HBsAg loss but identifies a potential therapeutic target for Peg-IFNα treatment. We believe our results are of great interest to a wide range of stakeholders based on their potential clinical implications.

The Future of (Radio)-Labeled Compounds in Research and Development within the Life Science Industry.

In this review the applications of isotopically labeled compounds are discussed and put into the context of their future impact in the life sciences. Especially discussing their use in the pharma and crop science industries to follow their fate in the environment, in vivo or in complex matrices to understand the potential harm of new chemical structures and to increase the safety of human society.

Die Zukunft (Radio‐)‐isotopenmarkierter Verbindungen in Forschung und Entwicklung der modernen Lebenswissenschaften

AbstractIn diesem Überblick diskutieren wir die Einsatzmöglichkeiten von isotopenmarkierten Substanzen und betrachten ihre zukünftige Relevanz für die Biowissenschaften. Insbesondere wird ihre Verwendung in der Pharma‐ und Pflanzenschutz‐industrie erörtert. Ihre wichtigste Anwendung ist die Verwendung als Marker in Wirkstoffen. Ihre strukturelle Veränderung wird in der Umwelt, in vivo oder in komplexer Umgebung verfolgt. Dies dient dazu, Auswirkungen neuer Wirkstoffe zu ermitteln und die Sicherheit für die Menschheit und Umwelt zu steigern.

Assessment of Triglyceride Droplet Crystallization Using Mixtures of β-Lactoglobulin and Phospholipids as Emulsifiers

Many applications in the life science and food industries require (semi-)crystalline oil-in-water (O/W) dispersions. Unfortunately, high supercooling and, thus, low temperatures are often needed to induce the crystallization of droplets. As low molecular weight emulsifiers (LMWEs) are able to act as nucleation templates, they might help to decrease the required level of supercooling. Furthermore, proteins and LMWEs are frequently co-formulated to improve the colloidal stability of emulsions and dispersions. Hence, choosing a suitable protein and LMWE mixture would allow for achieving specific product properties for controlling the solid fat content (SFC) and take advantage of the stabilization mechanisms of both emulsifiers. Therefore, this study focuses on the impact of the co-existence of β-lactoglobulin (β-lg) and phospholipids (PLs) LMWEs on the SFC of triglyceride (TAG) droplets at isothermal conditions using a thermo-optical method. When β-lg alone was used as an emulsifier, a maximum SFC of 80% was obtained at a supercooling of 32 K and 42 K for trilaurin and tripalmitin, respectively. The SFC could be increased to 100% using a PL containing saturated fatty acids (FAs) and a small hydrophilic headgroup. At the same supercooling, a PL containing saturated FAs and a large hydrophilic headgroup led to a maximum SFC of 80%. At lower supercooling, the SFC was reduced with this PL by 10% compared to β-lg alone. In addition, when the PLs had more time to adsorb and rearrange with ß-lg at the interface, even lower SFCs were observed compared to cooling directly after emulsification.

A theory on ICER pricing and optimal levels of cost-effectiveness thresholds: a bargaining approach.

In many health systems around the world, decisions about the reimbursement of-and patient access to-new medicines are based on health technology assessments (HTA) which, in some countries, include the calculation of an incremental cost-effectiveness ratio (ICER). Decision-makers compare the ICER against a pre-specified value for money criterion, known as the cost-effectiveness threshold (CET), to decide in favour of or against reimbursement. We developed a general model of pharmaceutical markets to analyse the relationship between the CET value and the distribution of the health and economic value of new medicines between consumers (payers) and producers (life science industry developers). We added to the existing literature in three ways: including research and development (R&D) cost for developers as a sunk cost; incorporating bargaining using the Nash bargaining solution to model payer bargaining power from regulation and use of competition; and analysing the impact of a non-uniform distribution of developers R&D costs on the supply of innovation. In some circumstances of bargaining power distribution and R&D cost, we found that using a CET value in HTA decision-making higher than the supply-side CET is socially efficient. Decision-makers should consider adjustable levels of the CET or interpretation of ICERs higher than the CET according to the bargaining power effect. The findings of this research pointed to the need for more research on the impact of bargaining power, how R&D investment responds to rewards, i.e. the elasticity of innovation, and pre- and post-patent expiry modelling.

The utilization of artificial intelligence in life science research and healthcare delivery

The goal of this research is to evaluate the effectiveness of the system for innovation and identify the reasons that prevent Artificial intelligence (AI) healthcare technology advancements connected to the life sciences sector from being implemented. To evaluate the structural and efficient dynamics of AI healthcare technology advances associated with the life science business in West Sweden, the socio-technical analytical framework of Technological innovation systems (TIS) was employed. Using a mixed-methods research methodology, the case study triangulates qualitative and quantitative information since subordinate distributed sources and discussions with twenty-one experts and twenty-five life science industry leaders. According to the findings, the functioning of the innovation system is largely constrained by its limitations, which include a lack of resources and inadequate statements from top healthcare experts about their requirements for advancing healthcare via the use of AI technological advances. This research demonstrates that to enhance the performance of the innovation system, governmental interventions aimed at expanding the pool of resources as well as creating vision and purpose statements for the advancement of healthcare via AI technology breakthroughs may be promoted. By using the socio-technical TIS paradigm in a hospital setting, this research advances our knowledge of the processes and interdependencies across system works

한국 바이오헬스 산업의 미국 수입거부 대응 방안 연구 : FDA 위반코드 분석을 중심으로

한국 바이오헬스 산업의 미국 수입거부 대응 방안 연구 : FDA 위반코드 분석을 중심으로

Effects of Cooling Rate and Emulsifier Combination on the Colloidal Stability of Crystalline Dispersions Stabilized by Phospholipids and β-Lactoglobulin

A lot of applications for (semi-)crystalline triacylglycerol (TAG)-in-water dispersions exist in the life science and pharmaceutical industries. Unfortunately, during storage, these dispersions are often prone to changes in particle size due to unforeseen crystallization and recrystallization events. This results in the alterations of important product properties, such as viscosity and mouthfeel, or the premature release of encapsulated material. In this study, we investigated the effects and interplay of formulation, i.e., emulsifier combination, and processing parameters, i.e., cooling rate, on the colloidal stability of dispersed TAGs and aimed to improve their colloidal stability. We chose phospholipids (PLs) and β-lactoglobulin (β-lg) as the emulsifiers for our model systems, which are commonly applied in many food systems. When dispersions were characterized directly after cooling, we obtained smaller particles and narrower size distributions after fast cooling. Over the course of eleven weeks, the creaming behavior, particle size, melting behavior and polymorphism were characterized. The dispersions stabilized with solely β-lg exhibited a slight increase in particle size, whereas a decrease in size was found when PLs were added. Our results indicate that mass transport phenomena between TAG droplets and particles took place during storage. This migration of TAG molecules changed the composition and size distribution of the dispersed phase, especially at higher PL concentration (0.1 wt%). In our case, this could be prevented by using a lower concentration of PLs, i.e., 0.05 wt%.

In whose pockets? How small Danish patient organisations balance legitimacy, representation and dependency in collaboration with public sector medical researchers and the life science industry

It is a commonly accepted idea that complex structural challenges can be solved if private actors, NGOs, and the public authorities collaborate (Brogaard in Politica 47(4):541–560, 2015), a view that has come to frame several publicly funded network activities in Denmark. This article takes its point of departure in one such project aimed at setting up a collaborative network between researchers, patient associations, and life science partners to stimulate growth in research and development. We analyse this project as a social arena with a focus on what is at stake for patient organisations in such a collaboration. Using social worlds and arena theory, we map the negotiation of discourses, images, and positions, thereby answering the questions: What kind of relationships emerge as patient organisations network with researchers and the life science industry in the name of patient centricity and how do patient organisations balance legitimacy, representation, and independence in such collaboration? We argue that patient organisations’ positions are expanding and taking new forms as they perform a balancing act, from which a ‘multiplayer position’ seems to have emerged. Lastly we propose that patient organisations’ complex interdependencies should be acknowledged, and introduce an understanding of ‘cumulative drives’ to capture the nature of these complexities.

Research on Intellectual Property Right Protection of Genetic Resources in China Under Benefit-Sharing

Genetic resources are the foundation for the development of the life science industry, and benefit-sharing is internationally defined as an important regime for the use of genetic resources for all mankind's benefit. In the strategy of strengthening intellectual property rights (IPR), China clearly states that IPR legislation of genetic resources should be done in due course, and that the system of IPR protection of genetic resources and the system of access to genetic resources and benefit-sharing should be improved. Presently, the legislation is scattered and abstract, with insufficient operability and international integration, so it's urgent to optimize. On the one hand, it is necessary to improve China's IPR legislation of genetic resources for adapting to the development of China's genetic resources utilization technology and the practice of creation based on genetic resources, and to use IPR protection of genetic resources to restrict the illegal access of other countries to China's genetic resources through the benefit-sharing mechanism. On the other hand, the rules on prior informed consent and source disclosure in foreign countries should be taken into account, so as to prevent other countries from illegally controlling Chinese genetic resources and their derivatives under strict IPR application procedures for genetic resources.

Streptavidin-Saporin: Converting Biotinylated Materials into Targeted Toxins.

Streptavidin-Saporin can be considered a type of 'secondary' targeted toxin. The scientific community has taken advantage of this conjugate in clever and fruitful ways using many kinds of biotinylated targeting agents to send saporin into a cell selected for elimination. Saporin is a ribosome-inactivating protein that causes inhibition of protein synthesis and cell death when delivered inside a cell. Streptavidin-Saporin, mixed with biotinylated molecules to cell surface markers, results in powerful conjugates that are used both in vitro and in vivo for behavior and disease research. Streptavidin-Saporin harnesses the 'Molecular Surgery' capability of saporin, creating a modular arsenal of targeted toxins used in applications ranging from the screening of potential therapeutics to behavioral studies and animal models. The reagent has become a well-published and validated resource in academia and industry. The ease of use and diverse functionality of Streptavidin-Saporin continues to have a significant impact on the life science industry.

A Microfluidic Approach to Investigate the Contact Force Needed for Successful Contact-Mediated Nucleation

Emulsions with crystalline dispersed phase fractions are becoming increasingly important in the pharmaceutical, chemical, and life science industries. They can be produced by using two-stage melt emulsification processes. The completeness of the crystallization step is of particular importance as it influences the properties, quality, and shelf life of the products. Subcooled, liquid droplets in agitated vessels may contact an already crystallized particle, leading to so-called contact-mediated nucleation (CMN). Energetically, CMN is a more favorable mechanism than spontaneous nucleation. The CMN happens regularly because melt emulsions are stirred during production and storage. It is assumed that three main factors influence the efficiency of CNM, those being collision frequency, contact time, and contact force. Not all contacts lead to successful nucleation of the liquid droplet, therefore, we used microfluidic experiments with inline measurements of the differential pressure to investigate the minimum contact force needed for successful nucleation. Numerical simulations were performed to support the experimental data obtained. We were able to show that the minimum contact force needed for CMN increases with increasing surfactant concentration in the aqueous phase.

Inhibition of VEGF-B signaling prevents non-alcoholic fatty liver disease development by targeting lipolysis in the white adipose tissue

Hepatic steatosis is a hallmark of non-alcoholic fatty liver disease (NAFLD), a common comorbidity in type 2 diabetes mellitus (T2DM). The pathogenesis of NAFLD is complex and involves the crosstalk between the liver and the white adipose tissue (WAT). Vascular endothelial growth factor B (VEGF-B) has been shown to control tissue lipid accumulation by regulating the transport properties of the vasculature. The role of VEGF-B signaling and the contribution to hepatic steatosis and NAFLD in T2DM is currently not understood. C57BL/6J mice treated with a neutralizing antibody against VEGF-B, or mice with adipocyte-specific overexpression or under-expression of VEGF-B (AdipoqCre+/VEGF-BTG/+ mice and AdipoqCre+/Vegfbfl/+mice) were subjected to a 6-month high-fat diet (HFD), or chow-diet, whereafter NAFLD development was assessed. VEGF-B expression was analysed in WAT biopsies from patients with obesity and NAFLD in a pre-existing clinical cohort (n= 24 patients with NAFLD and n= 24 without NAFLD) and correlated to clinicopathological features. Pharmacological inhibition of VEGF-B signaling in diabetic mice reduced hepatic steatosis and NAFLD by blocking WAT lipolysis. Mechanistically we show, by using HFD-fed AdipoqCre+/VEGF-BTG/+ mice and HFD-fed AdipoqCre+/Vegfbfl/+mice, that inhibition of VEGF-B signaling targets lipolysis in adipocytes. Reducing VEGF-B signaling ameliorated NAFLD by decreasing WAT inflammation, resolving WAT insulin resistance, and lowering the activity of the hormone sensitive lipase. Analyses of human WAT biopsies from individuals with NAFLD provided evidence supporting the contribution of VEGF-B signaling to NAFLD development. VEGF-B expression levels in adipocytes from two WAT depots correlated with development of dysfunctional WAT and NAFLD in humans. Taken together, our data from mouse models and humans suggest that VEGF-B antagonism may represent an approach to combat NAFLD by targeting hepatic steatosis through suppression of lipolysis. Non-alcoholic fatty liver disease (NAFLD) is a common comorbidity in type 2 diabetes mellitus (T2DM) and has a global prevalence of between 25-29%. There are currently no approved drugs for NAFLD, and given the scale of the ongoing diabetes epidemics, there is an urgent need to identify new treatment options. Our work suggests that VEGF-B antagonism may represent an approach to combat NAFLD by targeting hepatic steatosis through suppression of lipolysis. The neutralizing anti-VEGF-B antibody, which was used in this study, has already entered clinical trials for patients with diabetes. Therefore, we believe that our results are of great general interest to a broad audience, including patients and patient organizations, the medical community, academia, the life science industry and the public.