Defence, a publicly traded biotechnology company, is working to develop the next generation of vaccines, antibody-drug conjugates (ADCs), ADC products and therapeutic procedures to fight cancer using its proprietary AccumTM platform. At the core of the Defence Therapeutics platform is AccumTM technology, which enables precise delivery of pharmacologically relevant proteins to target cells and increases intracellular accumulation to those target cells. As a result, improved efficiency and efficacy against serious diseases such as cancer and infectious diseases can be achieved. With four new patents filed last year, Defence’s technologies have an increasing intellectual property portfolio. Research activities conducted by Defence last year and plans for future clinical trials will continue.
Core technology development
The core of the Company’s technology research is based on overcoming a major and common challenge that limits the efficacy of both vaccines and antibody-drug conjugates (“ADCs”). When the target cell binds and internalizes an antigen or an ADC, the complex becomes entrapped within small intracellular vesicles called endosomes. Over time, these endosomes undergo a maturation process, causing them to degrade before they can perform their respective functions. The company’s goal is to use the enhancing AccumTM formulation to improve the intracellular transport of biologic therapeutic agents by triggering their escape to cytosols, thus improving their therapeutic effect.
Effective cellular vaccine design.
AccumTM technology is ideally suited for vaccines. More specifically, antigens normally taken up by dendritic cells (“DCs”) – the best antigen-presenting cells in our body – are first entrapped in endosomes. As these endosomal organelles mature, the pH decreases (i.e., it goes into the acidic range,⁓4-5) to trigger the activation of specific enzymes as a means of initiating nonspecific antigen degradation. As a result, the resulting fragments can then pass through the endosomal pores to the cytoplasm where specific antigen degradation occurs by the proteasomal mechanism. Although this process occurs naturally, the generated antigen fragments are often damaged, making them unsuitable for optimal immune stimulation. By using AccumTM technology, the ingested antigens are preserved in their natural state while being transported to the cytoplasm. Thus, proteasomal degradation leads to a higher number of immunogenic and stable peptides on the surface of DCs, which can trigger effective T-cell activation.
In research activities conducted by the company, it was found that adding Accum-bound antigens to allogeneic DCs (AccuVAC-D001) increases the therapeutic effect of the vaccine and achieves a survival rate of 70-80% (compared to the 0-20% achieved by current experimentally tested DC-based vaccines). Following the completion of this study, Defence has signed an agreement with a clean room provider in Canada to conduct trial runs with its DC vaccine. The goal is to complete all required GLP studies by the first quarter of 2022 and conduct a Phase I trial against melanoma in the UK by mid-2022.
Development of protein-based vaccines for infectious diseases (COVID and HPV).
In parallel, the company has already completed all preclinical activities related to its COVID-19 vaccines. The first vaccine (DTC-PT001) is an injectable delivery form boosted by an adjuvant approved by the U.S. Food and Drug Administration (FDA). The data obtained showed a strong and durable production of IgG titers (more than 16 weeks) and achieved high reactivity against all tested variants. Moreover, the immunogenicity of the vaccine was well comparable between rodent (mice) and non-rodent (rabbits) models. In addition, vaccination of hamsters (third model – GLP study) followed by virus exposure resulted in effective protection with no observed side effects.
The second vaccine formulation (DTC-IN003) is a vaccine that blocks transmission to stop infection (as opposed to a vaccine that lowers the pathophysiology of the virus). In this case, the vaccine is administered intranasally with a special adjuvant (designed for intranasal vaccination). This vaccine not only triggered the production of IgAs at the mucosal surfaces (where the virus invades), but systemic immunity was also observed, and the antibodies produced showed cross-reactivity with all variants tested. A GLP challenge study is currently underway, with final results expected in late December 2021.
Another infectious disease vaccine in development at Defence Therapeutics is AccuVAC-PT009 against human papillomavirus (HPV). This vaccine uses a mixture of L1 proteins (from different HPV strains) in combination with AccumTM. This involves testing for the ability to produce antibodies against the HPV virus. The effect of the AccuVAC-PT009 vaccine will be compared to the commercially available Gardasil-9 vaccine in terms of immunogenicity (prophylactic vaccine). In addition, Defence is working on a second HPV-related vaccine, but targeted against cervical cancer (AccuVAC-PT0067). The goal of this vaccine is to modify both E6 and E7 proteins to covalently bind AccumTM and then test the vaccine for its ability to treat previously identified cervical cancer. Results of the preclinical studies will be available in early 2022.
Effective design of ADCs
One challenge of ADCs is insufficient intracellular accumulation of the chemotherapeutic agent transported for effective tumor killing. Defence demonstrated that AccumTM technology increased the ability of the ADC Kadcyla (T-DM1) to specifically kill breast cancer cells. AccumTMimproved endosomal escape of the ADC Kadcyla while targeting the nucleus. Defence anticipates that AccumTM technology will enable it to increase T-DM1 efficacy. This will allow the treatment to overcome resistance mechanisms such as reducing the number of receptors on the cell surface (thereby limiting the efficacy and transport of T-DM1 within the cell). The company has entered into a strategic collaboration with two European institutions to further develop its Accum-ADCs platform.
Responsible and sustainable action is firmly anchored in the WAGO Group’s corporate strategy. The company’s connection and automation technology is an important component of the infrastructure necessary to advance digitalization and energy efficiency, and thus contribute to global challenges such as decarbonization. The company wants to fulfill this responsibility together with customers and partners, but also within the company. Therefore, we have decided to consistently convert our vehicle fleet to alternative drives.
With a “Green Car Policy”, no pure gasoline or diesel engines will be permitted in the future. The medium-term goal is to purchase only zero-emission vehicles by 2025. By the end of this year, plug-in hybrids and electric cars will already account for 40% of the total fleet. The company’s pool vehicles, which are available for business trips at the German plants in Minden and Sonderhausen (Thuringia), will already be 80% electrified. In perspective, further concepts for sustainable mobility are to be incorporated into the policy.
“The consistent conversion of our vehicle fleet is a further step for us to make the energy transition possible together. If you want to act sustainably in the long term, you have to look at all aspects of your business. Here we can make a further contribution to saving CO2 for our company and achieve results quickly.”
– Axel Börner, Chief Financial Officer
In principle, teeth and gums can also be perfectly cared for with a normal toothbrush. However, dentists repeatedly find that most people find it easier to achieve good results with electric assistance, and are therefore increasingly advising electric brushes. TÜV SÜD product expert Andrea Mertl explains what consumers should look out for and how products are tested on the German market.
The figures speak for themselves: three quarters of all dentists in Germany are convinced that correct brushing is easier with an electric toothbrush; one in three even believes they can tell from their patients’ dentition whether they are using an electric brush or not. Today, around 40 percent of all people over the age of 14 in this country already use an electric toothbrush. Since this brushing method has long been taken for granted even by more and more kindergarten children, the market share will continue to grow significantly in the coming years. In addition, many electric fans from the very beginning are switching to new models. Here, it is not only product improvements in terms of program selection or battery charging capacities that are enticing – those who still use a retro model with an electric cord or battery operation should switch for safety or environmental reasons. New features such as a smartphone app that documents cleaning time and quality or recognizes which areas are being neglected via a connection to the camera also encourage new purchases.
Andrea Mertl is responsible for testing electric toothbrushes at TÜV SÜD: “Many manufacturers advertise that their products provide good brushing performance. With our tests, we check this on the basis of various aspects and ensure that the electric toothbrushes also clean gently, are user-friendly to use and comply with the specifications regarding safety and environmental protection.”
Innovative toothbrushing robot
An extensive test scenario has been defined for these reviews. A specially developed brushing robot has already been in use since 2017, simulating brushing performance on black-colored artificial dentures. A white paste represents plaque and impurities to be removed from the tested models. How well this is achieved is analyzed by software, which assigns scores for the criteria of interdental spaces, tooth necks, smooth surfaces and overall surface area during its evaluation. After these automated tests and, of course, a thorough safety check in which, for example, the cord and charging station are also closely examined, human test subjects of all ages come into play. They test several products from different manufacturers with different product features and from different price ranges. Only after this elaborate procedure does the company award its test seal.
Rotary model or sonic toothbrush
Basically, electric toothbrushes are based on two different technologies. Rotary models and sonic toothbrushes are still on the market, and within these groups there are of course differences in terms of functionality. Very good results can be achieved with both variants: Rotary brushes have a small, rotating round brush head that works on each tooth individually. The brushes brush with an alternating left-right movement – a semi-circular rotation of the brush head.
Sonic toothbrushes usually have larger, oval brush heads and clean a larger area at once. Nevertheless, the brushes do not clean with sound, but with vibrations that occur at a very high frequency. Meanwhile, the integrated transducers generate sound waves between 250 and 300 hertz that drive the brush head. This creates a buzzing sound, which originally gave this type of toothbrush its name. Since less pressure is required with this system, gentle cleaning is even easier and interdental spaces are also better reached, more and more users are giving preference to sonic brushes.
Special form of sonic brush: ultrasonic toothbrushes
Still relatively new on the market are ultrasonic toothbrushes, which use a special toothpaste and send tiny microbubbles into the deepest crevices of the teeth at up to 96 million vibrations per minute to loosen plaque and bacteria. While the results achieved are excellent, optimal cleaning takes significantly longer than with other systems. Moreover, at the moment this technology is still exclusively represented in the upper price segment and is mainly recommended for people with gum problems, braces or bridges.
“Whether a toothbrush with smartphone connectivity is really necessary is up to each buyer to decide. However, our experience shows that electric toothbrushes generally make good oral hygiene much easier. In any case, we advise to go for tested safety and to pay attention to the corresponding labeling when buying.”
– Andrea Mertl
More space in the control cabinet thanks to compact controller family
Now B&R is launching a new compact controller family called X20 Embedded. The devices combine performance and numerous integrated interfaces in a housing just 55 mm wide. This makes the controllers half the size of comparable devices.
Thanks to the powerful processors from the Intel Atom series, the new controllers are also suitable for demanding applications with short cycle times. The devices can even be used to control fully-fledged robot applications. Machine builders thus save costs and space in the control cabinet.
The controllers come standard with two USB ports, integrated flash memory and two Ethernet ports. Daisy-chain cabling can be easily implemented with the integrated switch. Therefore, there are no additional costs for the network infrastructure.
Hardware interfaces for POWERLINK and RS485 are also integrated in the devices. Via the RS485 interface, the user can, for example, connect frequency converters directly to the controller without any additional hardware. The power supply is also integrated. Despite the high performance, the controllers do not require a fan or battery and are therefore maintenance-free.
Optionally, any other fieldbus protocols can be added. For this purpose, the controllers are optionally available with an interface slot. All B&R interface cards can be combined with devices from the X20 embedded series. Likewise, all X20 I/O modules can be added to the controller as usual.