The new service is designed for the rapid production of Antibody-drug Conjugates or ADCs and is expected to help reduce the time needed to produce development grade constructs for target molecule identification and accelerate preclinical ‘best’ candidate selection.
MilliporeSigma, a contract development and manufacturing organization (CDMO), has more than 35 years’ experience handling biological molecules and small molecules, performing conjugation and complex analytical testing and manufacturing, reducing complexity for customers.
In this interview with ADC Review, Jyothi Swami, Associate Director, ADC/Bioconjugation Contract Manufacturing and Lisa McDermott, Director, Process and Analytical Development answer questions about ADC Express™ and how it will advance the development of ADCs.
Question: What are ADC Express™ services?
Answer: ADC Express™ services utilize an established platform technology for the rapid production of ADCs, which can reduce the time needed to produce development grade constructs for target molecule identification.
Q: What are the benefits/advantages of ADC Express™ services?
A: ADC Express™ services are designed to accelerate pre-clinical conjugation candidate selection, provide rapid production of antibody-drug conjugates for best candidate selection, and reduce time to clinical through comprehensive services that support pre-clinical to commercial production from a single source.
Q: How is this different from other approaches?
A: The key differentiator of this service platform is speed. Other approaches may involve the preparation of one ADC construct at a time that is time-consuming and can incur additional costs during the development process.
Q: How does this help academic and small biotech drug development?
A: Academia and small biotechs benefit from ADC Express™ services, as they don’t need to invest in the infrastructure required to prepare ADC constructs. In addition, they may not have the complete package of tools and expertise to prepare and test the constructs.
MilliporeSigma has produced more than 400 non-GMP manufacturing batches representing more than 45 different ADC constructs and manufactured more than 115 batches of cGMP materials. We are in a unique position to support smaller players who are lacking in infrastructure and expertise but are keen to move forward with their concept.
Q: One of the problems in the development of ADCs is that it often includes multiple sites and multiple (different) organizations. How do ADC Express™ services change this?
A: Typically, five to ten CDMOs spread across the globe are involved in the development and production of ADC programs. MilliporeSigma’s comprehensive service portfolio combines the crucial steps of the drug development and production: mAb solutions, linker, payload, and the final conjugation – all from a single source. In addition, ADC Express™ services use a medium/high throughput approach where multiple constructs with different conjugation technology can be prepared simultaneously, speeding up the construct preparation process.
Q: Are ADC Express™ services only available to existing MilliporeSigma customers?
A: No, these services are available to anyone who has the need for the preparation of multiple ADCs – this includes new and existing customers.
Q: What is the smallest and largest quantity that can be requested?
A: The smallest quantity that can be requested is 10 to 20 mg monoclonal antibody (mAb) input, and the largest quantity cannot exceed 100 mg mAb input. The amount of ADC delivered depends on the scale and technology platform; any request larger than 100 mg is not in scope for ADC Express™ services.
Q: Who will provide the linkers, payloads, and antibody?
A: MilliporeSigma will provide the Mertansine (DM1) payload and PEG linker, and other payloads such as PBDs and auristatins and corresponding linkers can be purchased as non-GMP material or supplied by the customer. The customer is expected to provide the antibody, however, if requested, MilliporeSigma can procure a non-GMP monoclonal antibody (mAb).
Q: How will the samples be shipped?
A: The samples will be shipped directly to the customer from our site in St. Louis, MO.
Q: Will there be any routine meetings with the customer?
A: The MilliporeSigma team will schedule one meeting to kick off the project and a second meeting after the samples have shipped.
Q: What process or testing information will be shared with the customer?
A: MilliporeSigma will use the platform process to generate ADCs, however only a certificate of testing will be provided. Data scans are not voluntarily offered; however, they can be included upon request.
Q: Will the process details be shared with the customer?
A: No, only minimal details will be shared with the customer (i.e. certificate of testing) – please see the response to question #11.
Q: Will there be any savings to customers if they decide to use MilliporeSigma for further development and GMP activities?
A: We are open to discussing cost savings for customers who decide to partner with us on additional development work. We can offer discounts on GMP work depending on how many ADC constructs are prepared.
Q: Can MilliporeSigma support additional testing of the ADC construct? If yes, how is the payment/proposal handled?
A: No, we do not support additional testing of the ADC construct. Based on our 35+ years of experience in the development and manufacturing of biologics, conjugation processes, and small molecules, we have identified the critical assays that will be performed on each of the prepared ADC constructs.
Q: Can the constructs involve drugs to FAB or nucleotide or other peptides, or do they have to be only with mAb?
A: Yes, the ADC constructs can involve FAB, nucleotides or peptides as long as the technology is possible.
Q: Does the customer have to use specific conjugation chemistry?
A: If the customer does not already have an established type of chemistry (Lysine/Cysteine conjugations), we will recommend a technology that is suitable for their mAb and linker/payload combination.
Benefit for developers
With the development, if ADC Express™, drug developers with a pipeline of monoclonal antibodies looking to enter ADC space, these new services allows them to obtain ADCs without having to invest in potent handling capabilities. What’s more, drug developers can either bring their own linker technology or procure a linker payload from MilliporeSigma. The approach confirms the company’s commitment to the development and production of ADC, combining the crucial steps of drug development and production – mAb solutions, linker, payload, and the final conjugation — all from a single source.