Periodic Reporting for period 1 - A2MStools (Tools to access and analyze un-reduced mass spectrometry data to accelerate access to biotherapeutics)
Reporting period: 2021-04-01 to 2022-03-31
The 2020-2022 COVID pandemic taught the entire society that our bodies deal with deadly viruses by producing the special defense molecules – antibodies. On the other hand, the antibodies themselves are the protein molecules that could be “on request” designed and produced outside of our bodies. In this case, the antibodies are referred to as “biotherapeutics” and constitute a critical life-saving class of drugs. Developing antibody-based drugs is one of the current powerful responses of our society to life-threatening diseases, such as cancer. However, the processes of antibody-drug development and drug quality monitoring are challenging scientifically and technologically.
Mass spectrometry is the analytical technique that can provide very detailed qualitative and quantitative information on the antibodies. It works by accurately weighing the antibody molecules as the whole and their parts and recording the data about the antibodies in the form of a “mass spectrum”. Due to the very large amounts of information contained in these mass spectra, companies that produce mass spectrometers tend to reduce the size of the files that contain information on antibodies by taking away some of the information. Therefore, the conclusions that can be drawn with this information are not as complete and not as accurate as could be without data reduction/truncation. For example, not all proteoforms of antibodies can be detected, with those present in the minor amounts missing from the reports. However, the minor components can be essential for the overall biological function and activity of the antibodies.
Moreover, even if the scientists had the special software tools that would allow them to extract information from the full or unreduced data (mass spectra), they would not be able to apply these software tools, as many of the modern mass spectrometers employed for antibody analysis do not provide these unreduced data – a limitation imposed by the instrument manufacturers. The latter is done primarily due to the technical challenges.
The A2MSTools project aimed to increase the amount of information that scientists can obtain about the antibody molecules by providing the access to the unreduced data from the mass spectrometers and by equipping scientists with the software tools for processing and analysis of these unreduced data sets. These capabilities were first developed as the innovations in the precursor EU initiative, the FET project TopSpec, and included an electronic device – FTMS Booster BioPharma – to access the unreduced data from the mass spectrometers and the software tools –Peak-by-Peak BioPharma and FTMS Simulator BioPharma – to process and analyze the unreduced (and reduced) data. The A2MSTools objectives were thus to evaluate the developed innovations in their operational environment – in the analytical laboratories equipped with the mass spectrometers that are used to analyze the antibodies. The project provided the answers to the practical questions – how to install these innovative products in the laboratories, what is their impact on the processes of antibody analysis, how are they considered by the scientists – would they use them? Moreover, the project also considered the business opportunity of bringing these innovations to the market – what are the competitors, what intellectual property rights are to be secured, and what are the potential markets and the end-users.
Mass spectrometry is the analytical technique that can provide very detailed qualitative and quantitative information on the antibodies. It works by accurately weighing the antibody molecules as the whole and their parts and recording the data about the antibodies in the form of a “mass spectrum”. Due to the very large amounts of information contained in these mass spectra, companies that produce mass spectrometers tend to reduce the size of the files that contain information on antibodies by taking away some of the information. Therefore, the conclusions that can be drawn with this information are not as complete and not as accurate as could be without data reduction/truncation. For example, not all proteoforms of antibodies can be detected, with those present in the minor amounts missing from the reports. However, the minor components can be essential for the overall biological function and activity of the antibodies.
Moreover, even if the scientists had the special software tools that would allow them to extract information from the full or unreduced data (mass spectra), they would not be able to apply these software tools, as many of the modern mass spectrometers employed for antibody analysis do not provide these unreduced data – a limitation imposed by the instrument manufacturers. The latter is done primarily due to the technical challenges.
The A2MSTools project aimed to increase the amount of information that scientists can obtain about the antibody molecules by providing the access to the unreduced data from the mass spectrometers and by equipping scientists with the software tools for processing and analysis of these unreduced data sets. These capabilities were first developed as the innovations in the precursor EU initiative, the FET project TopSpec, and included an electronic device – FTMS Booster BioPharma – to access the unreduced data from the mass spectrometers and the software tools –Peak-by-Peak BioPharma and FTMS Simulator BioPharma – to process and analyze the unreduced (and reduced) data. The A2MSTools objectives were thus to evaluate the developed innovations in their operational environment – in the analytical laboratories equipped with the mass spectrometers that are used to analyze the antibodies. The project provided the answers to the practical questions – how to install these innovative products in the laboratories, what is their impact on the processes of antibody analysis, how are they considered by the scientists – would they use them? Moreover, the project also considered the business opportunity of bringing these innovations to the market – what are the competitors, what intellectual property rights are to be secured, and what are the potential markets and the end-users.
Overall, the A2MSTools project confirmed the technical and operational feasibility of the innovations considered within the project for the biopharma applications. The gathered information allowed to reveal the unique and common features required for the modern analytical workflows and software tools to ensure their use in the biopharma industry and academic research institutions. The related protocols (including installation and operation) have been optimized based on the end-user feedback and suggestions. The considered innovations are thus suggested for the launch as commercial products, and the corresponding Business Plan has been proposed.
The work performed during the A2MSTools project included:
- Interaction with partners in biopharma industry and academic research laboratories, including visits to the analytical laboratories in Europe and the USA;
- Interaction with the key opinion leaders and analytical scientist at the in-person and virtual exhibitions and scientific gatherings, in Europe and in the USA;
- The in-person and on-line interaction with the analytical scientists for the in-depth demonstrations of the software products and supervised data processing activities;
- Marketing analysis and business plan development.
In line with these activities, the A2MSTools project produced the following exploitable results:
- Reports and protocols on the hardware benchmarking, technical feasibility, and operation: installation and analytical tests in the analytical laboratories of biopharma partners;
- Reports on the software installation, technical and operational evaluation;
- Evaluation reports on the integrated workflow for the analysis of antibodies;
- Short course materials on “FTMS Fundamentals and Data Processing”;
- Business Plan, including the marketing and competitor analysis.
The dissemination and communication of the results has proceeded via:
- Website creation and regular information content increase
- Regular updates and posts on professional social media (LinkedIN and Twitter)
- Scientific and user-oriented presentations at the on-line and in-person meetings
- Short course (on-line) and webinars / workshops
- Scientific papers in the peer-reviewed journals and reports
- Exhibit booths at the scientific and technical exhibitions, such as ASMS (USA) and Antibody Congress (Switzerland)
The work performed during the A2MSTools project included:
- Interaction with partners in biopharma industry and academic research laboratories, including visits to the analytical laboratories in Europe and the USA;
- Interaction with the key opinion leaders and analytical scientist at the in-person and virtual exhibitions and scientific gatherings, in Europe and in the USA;
- The in-person and on-line interaction with the analytical scientists for the in-depth demonstrations of the software products and supervised data processing activities;
- Marketing analysis and business plan development.
In line with these activities, the A2MSTools project produced the following exploitable results:
- Reports and protocols on the hardware benchmarking, technical feasibility, and operation: installation and analytical tests in the analytical laboratories of biopharma partners;
- Reports on the software installation, technical and operational evaluation;
- Evaluation reports on the integrated workflow for the analysis of antibodies;
- Short course materials on “FTMS Fundamentals and Data Processing”;
- Business Plan, including the marketing and competitor analysis.
The dissemination and communication of the results has proceeded via:
- Website creation and regular information content increase
- Regular updates and posts on professional social media (LinkedIN and Twitter)
- Scientific and user-oriented presentations at the on-line and in-person meetings
- Short course (on-line) and webinars / workshops
- Scientific papers in the peer-reviewed journals and reports
- Exhibit booths at the scientific and technical exhibitions, such as ASMS (USA) and Antibody Congress (Switzerland)
Each of the three innovative solutions addressed by the A2MSTools project enable progressing our abilities to perform analysis of antibodies beyond the state-of-the-art. The details on these advances can be consulted from our publicly accessible webpage: https://spectroswiss.ch/resources/(opens in new window)
The ease of use and automation of data processing routines offered by the unique algorithms in Peak-by-Peak BioPharma tool are particularly welcome by the biopharma industry, where the technical personnel may not have the required in-depth knowledge and skills to operate the comprehensive but complex data processing and analysis software. Naturally, Peak-by-Peak BioPharma solution is suitable for processing also of the regular, reduced, data from the mass spectrometers, as well as any size data from not only the FTMS instruments, but also from the widely employed time-of-flight (TOF) mass spectrometers.
The synergy of the integrated hardware and software workflows, as well as the stand-alone software solutions extend the state-of-the-art performance of biopharma workflows obtainable with the common hardware and software tools. The provided boost in the information translates into the corresponding boost in knowledge. The enhanced performance and productivity of mass spectrometry-based workflows increase the amount of work that can be performed with a single mass spectrometer by a single scientist or technical operator. Therefore, the saved funds or personnel and/or instrument time may accelerate the related drug development research and bring the new antibody-based drugs to us faster.
The ease of use and automation of data processing routines offered by the unique algorithms in Peak-by-Peak BioPharma tool are particularly welcome by the biopharma industry, where the technical personnel may not have the required in-depth knowledge and skills to operate the comprehensive but complex data processing and analysis software. Naturally, Peak-by-Peak BioPharma solution is suitable for processing also of the regular, reduced, data from the mass spectrometers, as well as any size data from not only the FTMS instruments, but also from the widely employed time-of-flight (TOF) mass spectrometers.
The synergy of the integrated hardware and software workflows, as well as the stand-alone software solutions extend the state-of-the-art performance of biopharma workflows obtainable with the common hardware and software tools. The provided boost in the information translates into the corresponding boost in knowledge. The enhanced performance and productivity of mass spectrometry-based workflows increase the amount of work that can be performed with a single mass spectrometer by a single scientist or technical operator. Therefore, the saved funds or personnel and/or instrument time may accelerate the related drug development research and bring the new antibody-based drugs to us faster.