Payloads and Linkers

Selection of a proper payload-linker (also known as drug-linker, toxin-linker or linker-payload) is essential. At NJ Bio, we add value by not just offering high-quality payload-linkers, but also by helping in the selection of the most appropriate one based on the biology of the target. Our experts can help identify a screening cascade to move from early discovery to finding a clinical candidate. Our extensive chemistry and ADC experience allows us to mix and match a variety of linker and payload technologies to maximize the clinical properties of the resulting bioconjugate. Being an advisor and partner is an important part of the work we do. NJ Bio can also provide scale-up and development of payload-linkers to help accelerate the synthesis of your clinical candidate. Having a partner like NJ Bio with deep bioconjugation and chemistry know-how can add tremendous value in the selection and development of bioconjugate therapeutics.

Discovery Payload-Linker Services

NJ Bio’s Payload-Linker Design Process

We can help at different stages of the R&D process and select the fastest pathway to developing a bioconjugate clinical candidate. We supply validated as well as custom and novel linker-payloads. We can support chemical scale-up and development of linker-payloads. NJ Bio can create value when new, custom and challenging chemistry is required. Contact us to see how we can bring value to your program(s).

Validated Payload-Linkers

We have a variety of payloads and linkers that are clinically validated and can be used to see how the bioconjugate behaves regarding efficacy, potency, and physical properties. The advantage of having known payload-linkers is that you can rapidly determine whether a payload gets complete tumor regression and how well the bioconjugate performs in vitro and in vivo. We can perform rapid conjugations and test the conjugates in vitro to help accelerate discovery through our integrated synthesis and bioconjugation services. Validated combinations such as MC-VCP-MMAE (vedotin), SMCC-DM1 (emtansine), SPDB-DM4, DM21C, MC-MMAF (mafodotin), PBD dimers (tesirine and talirine), camptothecins (deruxtecan) and SN38 (govitecan), IGNs (DGN549C), and many others are readily available for conjugation and can be rapidly synthesized in larger quantities. The payloads and/or linkers are also available as individual units. This service is also used for benchmarking new antibody or conjugation technologies against current standards.

Custom Payload-Linkers

Not all validated and approved payload-linker combinations are optimal for a given protein or indication. The resulting conjugate may be too hydrophobic, be outside the required potency range, or the release mechanism might not be appropriate. Our extensive experience and synthetic capabilities allow us to tailor the most promising linkers and payloads for a given protein/mAb using the latest technologies. Selecting linker-payloads with good solubility, activity and release kinetics can deliver clinical activity at the expected clinical dose range. Such optimization can make the difference whether the bioconjugate will be successful or require an expensive late stage redesign.

Novel Payload-Linkers

If you have a new release mechanism or a new payload that could require unique chemistries, our synthetic experience can accelerate the preparation of these novel entities. Our expertise can also help expand the chemical space to carve out new intellectual property which would be owned by you. This novel space and linker exploration is usually accomplished within a year and can yield equivalent or better activity to what is currently state of the art. If timed properly, this can result in minimal delays when performed in conjunction with other development activities. A general bioconjugate platform can also be created that augments your biologics pipeline.

Scale-Up

Knowledge of precedented and novel linker-payloads allows us to develop rapidly scalable routes to challenging compounds in batch and flow processes. We have worked out many chemistry solutions to challenges that usually hinder chemical development of linker-payloads. We have invested in flow chemistry which helps with containment of highly potent compounds and allows us to scale and produce these materials in a smaller footprint. Flow chemistry is well-suited to enhance safety, scalability, and cost-effectiveness of linker-payload manufacturing. Even with all the advantages of flow, you might still desire a batch process which we can develop and support.

Development Support

Our expertise in synthesis allows us to help you identify and validate small molecule impurities. We can generate specialized and critical reagents needed for PK and other supporting assays required for clinical development. All these development activities can be included in your IND submission.

cGMP Suites

We are working on expanding our services to manufacture material for IND-enabling studies and phase 1 and 2 clinical trials. These cGMP suites are scheduled to be operational in 2Q 2023.

Frequently Asked Questions

• How do antibody-drug conjugates work?
• What kind of linkers are used for ADCs?
• What kind of toxins & linkers are used for ADCs?
• What kind of payloads are used in ADCs?
• Which ADCs are on the market or in pivotal trials?

Click here for review articles for antibody drug conjugates