The benefits of using a single-source for discovery, development and GMP manufacture of antibody drug conjugates and other novel bioconjugates
WUXI XDC – OFFERING A STREAMLINED PLATFORM FOR ADCS AND OTHER BIOCONJUGATES
I began the podcast by asking Jimmy if he could talk about the formation of WuXi XDC and why they decided to form the company. He explained that there were several reasons, but the overriding factor was to offer clients a more seamless, streamlined technology platform to enable them to bring their complex bioconjugate drugs to the market more efficiently and cost-effectively.
Next, I asked him to elaborate on how the formation of WuXi XDC could accomplish these goals. He stated that for many years WuXi Biologics has provided industry-leading single-source, concept to commercialization platforms for antibodies and other biologics, and WuXi Biologics also offered extensive conjugation development and GMP manufacturing capabilities for ADCs and other bioconjugates. Likewise, WuXi STA provided one-stop services from discovery to GMP manufacturing of the chemical entities that comprise the payloads and linker intermediates used in these complex biotherapeutics. By bringing all these capabilities and capacities under one organization, they are greatly simplifying the drug development process.
I then asked about the benefits to clients. We discussed how it helps clients from a time and cost perspective. The client has only one contract and one company to manage and audit, one streamlined development platform, one project management system and an organization with sole accountability for the entire product development program. Also, what makes WuXi XDC unique is that all these capabilities are within minutes and at best a couple hours from each other.
I asked Jimmy to clarify why geography was important. He said that when working with a collection of service providers, the ADC development and manufacturing is generally spread across countries and continents even, which is a potential source of risk and can add significant time to the overall project. For instance, the payload/linker might be manufactured in China, the antibody in the U.S., and the conjugation or drug product produced in Europe. WuXi XDC provides an unprecedented, geographically dense product development and supply chain.
I asked about where WuXi XDC facilities are located. He said that the antibody intermediate and bioconjugation R&D and CMC development can take place throughout multiple facilities in Shanghai or Wuxi city in China, as they have large teams dedicated for those activities in both locations. The payload-linker R&D, process development and GMP manufacturing is conducted primarily in Changzhou, but an additional facility is also available in Shanghai. All those locations then transfer the final processes or intermediate products to Wuxi city where the production of the bioconjugate drug substance and drug product takes place in their state-of-the-art GMP facilities. Other supporting activities like preclinical DMPK, toxicology, cell line characterization and viral clearance also are close by in the city of Suzhou.
BENEFITS OF A ONE-STOP SOLUTION FOR ADC DISCOVERY, DEVELOPMENT, AND GMP MANUFACTURE
Next, we discussed that the perceived challenges of one-stop offerings is that the expertise or quality may not be the same across all facets of the organization. He described how WuXi XDC is addressing this concern by bringing multiple experts with 10-30 years of experience in each aspect of bioconjugate R&D, manufacturing, and quality, to lead their teams. They also have an extensive scientific training program for all new scientists and engineers that includes classroom instruction, mentoring, shadowing, and hands-on training before they work on any project.
I asked how this could be measured. Jimmy said that they keep metrics of their performance across all disciplines, but ultimately, he believes the proof is in the high level of repeat clients and the number of clients that they have helped bring their bioconjugates into the clinic and beyond. He shared that they have over 100 global partners working with them on projects at various stages, and in just the last few years they have helped their clients bring 16 ADCs into the clinic, with 6 of these programs now in late-stage clinical trials or near BLA-filing stage.
GROWTH AND MARKET POTENTIAL OF ADCS
We then talked about ADCs as a unique drug modality and the overall market potential. Jimmy stated that a large driver in the formation of WuXi XDC was the future promise and potential market size for ADCs and other bioconjugates. He talked about how the market has grown steadily and has accelerated in recent years. Currently there are 14 ADCs worldwide that have been approved for commercial use, over 100 ADCs in various stages of clinical trials, and more than 150 in preclinical development. Based on various market research reports, it is estimated that commercial sales of ADCs could grow 25 to 35% annually for the next 5 to 10 years. In addition, based on drug company pipeline data, it appears that this trend will continue into the foreseeable future. As WuXi XDC’s mission is to provide open access drug development platforms so that every drug can be made, and every disease can be treated, they believe that the formation of WuXi XDC could uniquely support and enable all ADC drug developers through their single-source platform, expertise, vast capabilities, and resources.
I asked about the ability of WuXi XDC to scale to meet expected market demand growth in the future. Jimmy said that their ADC manufacturing supply chain includes antibody, payload-linker and bioconjugation drug substance and drug product. There is already substantial capacity now and planned for the antibody and payload-linker intermediates. Their current bioconjugation GMP facility for drug substance and drug product, which is part of a state-of-the-art integrated Biologics Conjugation Solution Center in Wuxi city, has the capacity to handle a wide range of bioconjugation projects now and over the next few years. This center, which consolidates all bioconjugate R&D and GMP manufacturing on one campus, will also include a new purpose-built commercial manufacturing plant for bioconjugates in the near future. They will be ready to support new and all existing clients currently in early-stage clinical trials with commercial supply if and when their products are approved.
SOLVING ADC PRODUCTION CHALLENGES AND SHORTENING TIMELINES
We then discussed the challenges of providing key antibody and chemical payload intermediates for an ADC and the expertise and facilities required. Jimmy said that by producing the joint venture of WuXi XDC between WuXi Biologics and WuXi STA they are bringing the entire value chain of activities from discovery to GMP manufacturing for the biologics and chemicals under one roof. That value chain includes library generation, screening, evaluation, preclinical assessments, CMC development, and GMP manufacturing resources from these two very large organizations. They even have, and are continuing to build, an inventory of common payloads and linkers that could be used for any bioconjugate program. Their payload and linker manufacturing sites include GMP high potency (HP) labs that can produce compounds with an OEL limit down to 10 ng per cubic meter.
I asked about the importance of having a true single source and whether it was an issue for drug developers in the past. He said that ADCs are very complex and to develop an ADC in the past typically meant that you needed separate CDMOs for the antibody, payload, linkers, bioconjugate, and drug product. In addition, separate vendors were often required to handle the preclinical activities like DMPK or toxicology, and specialist organizations to work on potency assays, or the critical biosafety testing elements such as viral clearance and cell line characterization. Managing the R&D effort and supply chain was a huge challenge – it required extensive time and personnel resources, and using multiple vendors meant adding more risk and the potential for intellectual property drift. The traditional timeline for bringing an ADC to the IND filing stage was anywhere from 24 to 30 months, or even longer, using the multi-vendor model.
I followed up about the long timelines to get ADC drugs into the clinic and asked how a single source model can help reduce timelines. Jimmy explained that you reduce all the time lost in project hand-offs between these vendors, and should there be project hurdles or changing requirements, they can be dealt with much faster if using a single source. WuXi XDC, via comprehensive project management, and through focusing on streamlining each step with deep understanding of all the individual process steps, has developed an ADC development platform that has cut the traditional development timeline in half. They offer clients a 15 month or less DNA to IND timeline for ADC therapeutics.
I closed by asking what XDC stood for. Jimmy explained that even though ADCs dominate the bioconjugate landscape, they wanted to communicate to the market that their service platform supports a wide variety of bioconjugated approaches such as oligo, peptide and pegylated conjugates. The “X” represents anything that drug developer’s imaginations and ingenuity believe can have a positive impact in patients’ lives. Jimmy concluded with “we’re here to help them, as our vision statement states, by linking innovation to health.”
Don’t miss part two of the interview with Dr. Li which can be found here. In the second podcast, we explore in greater detail why one-stop drug development organizations greatly streamline a pathway to the clinic and learn about new technologies available to make the development of ADCs more efficient and effective.