Chemical structure of “emtansine” (mertansine plus linker) linked to a monoclonal antibody (maytansine black, mertansine modification red, linker blue.
The excitement around ADCs for treating cancer stems from the realization that traditional, small-molecule cytotoxic drugs and radiation are still some of the most potent anticancer agents, and that targeting them by tethering them to antibodies might bypass some of the side effects.
The recent founding investment by Johnson & Johnson of the ADC-focused startup, Fusion Pharmaceuticals, may provide some momentum to the development of targeted radiotherapeutics, a specific type of ADC. Johnson & Johnson’s investment followed on the heels of recent ADC investments by other large pharmas, including Boehringer Ingelheim and AstraZeneca. IMMU-132, the ADC being developed by Immunomedics, and SGN-LIV1A from Seattle Genetics are ADCs that are reported to target triple-negative breast cancer.
The biopharmaceutical industry currently has over two dozen ADC candidates estimated to be in its pipeline, indicating that there is a current demand for scientists with specific expertise in the techniques required for designing, synthesizing, and studying these molecules. In addition to developing expertise in-house, companies are frequently partnering with smaller companies or outsourcing projects to service providers to get the work done.
At Science Exchange, we have a unique bird’s-eye view of ADC-focused research and the service providers that are facilitating progress in this exciting field. Researchers who order services using the Science Exchange marketplace gain rapid access to an innovative network of 3,000+ service providers, including a number that supports ADC studies, through a single contract with Science Exchange. In this blog post, we’ll go through some of the key techniques and show how featured service providers in our network are meeting needs of ADC researchers.
Key techniques for studying ADCs: Science Exchange service providers step up.
Target discovery: the abundance challenge
Many ADC research programs seek to target cell surface proteins that are unique to the cell type that is to be killed by the cytotoxin. However, cell surface proteins, and other ADC targets, are usually low in abundance and underrepresented in traditional proteomic measurements.
One of the newest, cutting-edge providers on the Science Exchange network is Biognosys, offering discovery proteomics solutions based on Hyper Reaction Monitoring (HRM-MS™), a Next Generation proteomics technology. Invented at Biognosys, HRM-MS delivers quantification of up to 9’000 proteins per sample across treatments or conditions and identifies significantly regulated proteins. This platform is ideal for ADC target discovery studies, with one proof-of-concept study showing the quantification of over 500 cell surface proteins from matched biopsy samples.
The conjugation challenge
The ideal linker between the antibody and the cytotoxin drug is stable in the bloodstream, and if needed, can be cleaved in the specific environment of the target. Some ADC linkers are designed to dissolve the the reducing environment of the cytosol, while others require specific enzymes of certain subcellular compartments. Other linkers are non-cleavable. The linker also has to have minimal toxicity.
In addition to some wizardry in chemical synthesis, ADC development therefore requires experience in cell-based assays and drug metabolism studies. WuXi Apptec, MabPlex, and ChemPartner are service providers listed on the Science Exchange marketplace that have worked side by side with ADC developers on all aspects of linker synthesis and characterization.
Conjugation-related services that WuXi Apptec, ChemPartner and MabPlex provide include but are not limited to:
- Cytotoxin development
- Linker development
- Linker and cytotoxin conjugations
- Drug linking site determination
- Stability studies for ADC products
Bioanalysis in ADC development: the heterogeneity challenge
Unlike other categories of drug molecules, ADCs can be structurally heterogeneous, because of dynamic drug:antibody ratios (DAR) and variations in linker attachment chemistry. In a recent survey, 69% of researchers cited this structural heterogeneity as the #1 challenge facing bioanalysis in ADC development.
85% of the surveyed researchers reported using LC-MS for ADC bioanalysis. However, over 24% respondents had to adapt traditional LC-MS methods, using affinity capture LC-MS or accelerator MS. 42% of respondents reported using ligand-binding assays, illustrating that most researchers use more than one technique in analyzing ADCs. The complexity of analytes, in combination with the lack of regulatory guidance around ADC analysis, have resulted in the need to use multiple, individually developed, methods.
Fortunately, the Science Exchange marketplace features the services of Biognosys, Anaquant, and ChemPartner, all of which provide experience in developing analytical methods for ADCs.
To address the challenge of quantifying multiple species per sample, Biognosys provides targeted proteomics services using Multiple and Parallel Reaction Monitoring (MRM and PRM), which are techniques that offer highly specific and sensitive multiplexed quantification of selected proteins from complex biological samples. These techniques deliver absolute or relative quantification of up to 150 target proteins per run with a dynamic range of 6 orders of magnitude.
Countless other service providers, such as Bio-Synthesis, Bionova, and Maine Biotechnology Services, are experts in analyzing ADCs using ligand-binding assays. In addition, Science Exchange’s in-house regulatory compliance team has expertise in working with representatives from regulatory agencies, to ensure that the analytical services carried out by our service providers meet necessary requirements.
ADC bioanalysis services on the Science Exchange marketplace include:
- DAR (drug:antibody ratio) determination
- Residual free drug analysis
- Pharmacokinetics (PK) determination
Process development for ADC
Again, the heterogeneity of a batch of ADC can make it challenging to develop a scalable, reproducible, and robust manufacturing process. Manufacturing the antibody component of the ADC faces all the same challenges as does traditional therapeutic mAb production.
Given the demands of manufacturing, engineering quality by design is important in the nonclinical, preclinical and early clinical phases of ADC research. Expertise in antibody optimization, protein purification, and chemical synthesis are required to create less heterogeneous batches of antibodies, linkers, cytotoxins and conjugates.
Science Exchange service providers WuXi Apptec, MabPlex and ChemPartner all support ADC process development, with MabPlex’s services extending to GMP and scale-up (to kilogram scale).
Browse our marketplace for ADC-related services or contact our Concierge Service, who can match your project needs with the right service provider or a combination of service providers to move your ADC research forward.
Researchers requesting services who have recently logged in to your Science Exchange account may have noticed the improvements we have made to your Dashboard! We hope that these changes will make it even easier to communicate with your service providers, manage projects, and compare quotes. Ultimately, our goal is to help you make better decisions, faster, with maximum transparency.
In this post, we summarize what is new in the dashboard for requesters.
Request services even more easily
If you have not yet requested services through Science Exchange, the new dashboard makes doing so as easy as possible.
Use the Marketplace for fastest access to providers. Type keywords into the Marketplace search bar, such as “ELISAs,” “Boston BioSource,” or “Cambridge MA,” to search our network of service providers. Requests are sent directly to the providers, giving you the fastest access to our network.
Enjoy white-glove sourcing with our Concierge service. Ask our Concierge service to find service providers by submitting the short webform. This will engage our Masters- and Ph.D.-trained Sourcing Managers, who will gather quotes from the best service providers for your project.
Track requests at a glance
Spend more time on science, less time monitoring your request status. Once you have made requests, the new Dashboard delivers a consolidated view to help you keep track of:
- Request status
- With whom you are working
- Both Marketplace and Concierge projects
As you can see below, the Dashboard makes it easy to identify and communicate with the people with whom you are working, for each project. If you have experience outsourcing research projects, you know well that better communication is key for obtaining reliable study results.
Brand new to the Dashboard is the addition of the Concierge Requests panel, which allows you to track your submitted projects. Once a Sourcing Manager has been assigned, their contact information will be displayed. Please reach out to your Sourcing Manager directly for updates on your Concierge requests.
Easily find the Marketplace request you are looking for
Once you have submitted numerous requests, you will find it useful to navigate from the Dashboard to the new Marketplace Requests page by clicking on “Marketplace Requests” to view them all. Here, you now have fine control over the way you view and manage your ongoing requests.
This page enables you to:
- Archive: Clean up your view by hovering over an individual request and clicking the archive icon. Archived requests will be excluded from the default view, but can still be found.
- Search: Quickly find your existing requests using any keywords.
- Filter: Narrow your view to requests of a specific status, or reveal archived orders.
- Sort: Arrange your orders either by Request Number (which orders them by creation) or by date of last activity.
Any questions? We would love your feedback on this long-anticipated improvement to our site.
Contact Science Exchange today!
One of the best advertisements for a product or service is a positive review from another customer. Reviews and ratings are so compelling and commonplace, they help guide our choices in car repair, travel destinations, and sushi restaurants. We think customer feedback is also incredibly useful when trying to find the right scientific service provider. For this reason, we began collecting Net Promoter Scores (NPS) from our clients and sharing them on supplier storefronts.
What is a Net Promoter Score? In 2003 Bain & Company launched a new way to gauge customer loyalty and satisfaction by creating a feedback survey with a single question: “What is the likelihood that you would recommend Company X to a friend or colleague?” Respondents answer this question on a scale of 0-10, with 10 being extremely likely and 0 being not at all likely. Based on their response, customers who provide feedback are placed into one of three categories:
- Promoters (9 or 10) are very satisfied clients who would urge others to buy from/work with the business
- Passives (7 or 8) are satisfied, but unenthusiastic about their experience
- Detractors (0-6) are unsatisfied customers who would share negative experiences about the company
The total Net Promoter Score is calculated by subtracting the number of detractors from promoters. Identifying three key groups within a customer base allows for more targeted interaction with clients. If someone marks a 6 or below, the company can follow up with that person and try to correct what went wrong.
We took that idea and applied it to our feedback surveys for service providers. Our rating system now includes detailed reviews contributed by other customers, as well as NPS information on each storefront. We understand outsourcing decisions aren’t only based on price, but finding a service provider you can trust to conduct experiments vital to the success of your research. In order to learn about our customers’ experience with a lab we ask the following questions:
- What is the likelihood that you would recommend (service provider) to a friend or colleague (0-10)
- How satisfied are you with the timeliness of the deliverables (0-10)
- How satisfied are you with the quality of the deliverables (0-10)
Integrating information like this on our platform is just one of the many ways Science Exchange provides industry insights that allow you to reduce risk when contracting with external service providers. To read reviews and find the NPS information for a service provider, click on the Ratings tab on any storefront, as seen here.
Science Exchange empowers researchers to work with confidence and make informed outsourcing decisions across all industries. Search our Marketplace to choose from thousands of screened labs and feel free to add a review of your experience. The unique feedback and NPS data you provide can help other teams find the right service provider for them.
Find the right service provider for you and start your project today.
For many people who use Science Exchange, a visit to the homepage is the first step in accomplishing their research objective. For requesters, service providers, or anyone using our network, the web experience is a crucial part of each project. With that in mind, we are excited to announce that we have refreshed the site, including an entirely new homepage. We have kept the same handy tools you will need to start and manage your research project, but improved the look and feel of some key pages. Search our marketplace for thousands of Science Exchange Verified Providers and request a quote in minutes. If your project is more specialized, you can partner with one of our staff scientists to find a perfect fit for your research needs with our concierge service. Every project is covered by the Science Exchange Guarantee, ensuring that your research can begin quickly, safely, and with complete IP protection. Science Exchange is an ideal partner for researchers who want to focus on science instead of sourcing, and progress instead of payment terms. We work with the world’s best suppliers to make scientific discovery faster, easier, and more reproducible. Providing scientists with a single relationship which manages compliance, contracts, and payments allows them to focus on the research goal at hand while collaborating with our cutting-edge providers. We think breakthrough discoveries should happen at the rate of science, not protracted negotiation. Take a look at our ever-growing network to explore how we can help with your next project.
At Science Exchange, we want to make it easier to find the best service providers to help you with your project. Our product development team has built features such as a search box that displays results as you type, and search results that are filterable to help you quickly find what you are seeking. These features are powered by a core search algorithm that references important service provider-specific information to rank the search results.
Once you enter a search, the algorithm determines the relevancy of search results based on the keyword you entered. The algorithm then looks at the service provider storefronts that pass through this filter and ranks them based on a service provider score. This score is calculated by looking at the following features:
Because we want requesters to hear back as soon as possible, service providers that respond to requests for quotes in a timely fashion have higher scores. We value providers who have consistently responded to their requests quickly. Plus, it is the polite thing to do. You are never penalized for declining requests. Declining a request is considered responsive behavior.
The service provider that regularly and consistently completes orders has a higher score and will rank higher in the search results. Requesters are more comfortable working with proven providers. If you are a provider, learn more about sending your own quotes to help boost your productivity quotient.
At Science Exchange, we offer people the chance to review service providers, and those that have many good reviews are ranked higher in the search results. However, we also take into account how long a service provider has been on Science Exchange. If you request a service from a lab, please write a review after the project is finished. If you are a service provider, please solicit recommendations from the requesters with which you work. You can also ask previous collaborators for endorsement; learn more.
New Lab Boost
We value our long-time Science Exchange service providers, but we also want to introduce new providers to the community effectively. Therefore, new providers receive a rankings boost during the first month after they join Science Exchange. If you are a service provider, take advantage of this boost by responding quickly to any requests and ideally completing projects so that when the boost goes away at the end of the first month, you will still appear high in the search results.
We will continue to optimize the search experience on Science Exchange. Check this blog regularly to stay informed of any changes.
This blog post is a guest post from Edword Simpson, technical engineer at Science Exchange lab, RS Calibration.
Ensuring that everything in your laboratory is ready for any upcoming audit is a nail-biting task. The annual FDA audit for compliance with regulatory guidelines, like the current goods manufacturing process (cGMP) is especially tedious. Manufacturing processes and equipment for pharmaceuticals are regulated very carefully by the FDA and require strict adherence to industry standards.
Here are five things that aren’t always given the attention they require and could easily result in regulatory action for failing to comply with cGMP: Read the rest of this entry »
Here at Science Exchange, we aim to enable efficient scientific collaboration. One of the biggest hurdles researchers face on our site is deciding where to send their requests. Conversely, it can be frustrating for lab admins to receive requests outside their capabilities. With that in mind, we are working on improving our search experience. This update will be available at the end of next month.
In preparation for our improved search experience, we’ve launched a tagging feature for labs. Labs can apply tags, such as equipment names, to their services, which will allow researchers to narrow their search to only labs that have the machine they need. Also, labs that have signed agreements with Science Exchange, like our Non-Disclosure Agreement, will receive storefront tags, allowing researchers who require that level of protection to quickly identify appropriate labs.
If you’re a lab admin on Science Exchange, we encourage you to begin tagging your services and storefront now! This will ensure that researchers will be able to find your lab more easily with our new search experience.
Read the rest of this entry »
Today, we’re excited to introduce a new, centralized order management experience on Science Exchange, focused on improving collaboration and messaging.
We take feedback from our researchers and labs very seriously and have designed the new order management experience with your input in mind. The new design, which went live earlier today, moves messaging front and center and introduces a timeline of all events.
A collaborative workspace
The new workspace allows researchers and lab members to intuitively collaborate on orders. Any member of the lab can see all messages on an order, enabling multiple members of the same lab to coordinate easily and efficiently under this team view. Everyone who has access to this order is shown on the righthand side.
Communication is key
Since open communication between researcher and lab is of utmost importance, the new order page focuses heavily on messaging. Messages and files can be sent during any stage of an order, from the top of any page. Users can start sending messages as soon as a request is posted, and continue sending them even after an order is complete. As always, there is no limit on the size or quantity of uploaded files. All messages and files appear in the main Timeline tab, along with all other events.
Keep track of your order
It can be difficult to keep track of research projects, so we’ve made it easy for you. The main timeline shows everything that has happened in reverse chronological order. You can always reference the order status indicator in the upper right hand corner. All available actions, like shipping samples or accepting a quote, are shown below the indicator for easy access.
Easy access to the latest details
Because research projects are updated regularly, we’ve added the Order Details tab. Here, you can always see the latest version of the order, no matter what state it is in. You can also download quote summaries and billing documents from the Files tab.
We think you will find that the rest of your overall workflow is largely the same, just more beautiful and intuitive. As of this morning, all orders will reflect the changes. If you have any questions, please don’t hesitate to reach out to us at email@example.com or share feedback.
About the author
Becca joined as Science Exchange’s first Product Manager, excited to help bring efficiency to scientific research. She previously launched SurveyMonkey Enterprise and WePay Canada. She has a degree from Stanford in Mathematical & Computational Science and enjoys cooking and home improvement in her spare time.
Just a few weeks ago, we introduced you to our new quotes with line items. There has already been another exciting development for the site and we want to share that with you as well!
Lab-Initiated Quotes, or LIQs (“licks”) as we affectionately call them, are a way for any lab to begin their interaction with a researcher by sending a quote directly to them, whether they are already on Science Exchange or not. Some terrific applications for LIQs are in cases when you’ve been discussing the scope of work with a researcher over email or the phone and want to send them a quick quote so they can accept and get the ball rolling on the project as soon as possible. Read the rest of this entry »
This has been an incredible year for Science Exchange. Our team has grown and our site is continually improving based on feedback we receive every day from researchers and lab admins alike.
Our newest feature was one of the most commonly requested from the lab admins on our site. It began as a discussion with the Lab Advisory Board – the LAB for short.
Previously, lab admins were able to submit text in a large description box, upload any pertinent files (like their institution quotes that included line items), and a price for the project. So in order to make the quoting process more flexible and intuitive, we’ve built line items into our existing quote system.
Labs are now able to generate their own line items within Science Exchange!
Read the rest of this entry »