Q&A: Overcoming ADC Challenges with Abzena’s ThioBridge Platform
EPM Editor Jai McIntosh recently caught up with Campbell Bunce, Chief Scientific Officer and Cambridge Site Head at Abzena to discuss Abzena’s ThioBridge technology.
Jai: Could you please explain what Abzena’s ThioBridge technology is?
Campbell: Abzena’s ThioBridge is a type of linker technology enabling the production of innovative bioconjugate therapeutics through the attachment of payloads to proteins containing cysteine bonds. In drug development, the protein chosen is typically an antibody, receptor or ligand that specifically targets a particular location and cell type in the body. Through bioconjugation, a payload can be linked to the protein to enable its delivery precisely to the target site.
Linker technologies are critical components in the development of antibody-drug conjugates (ADCs) with cytotoxic payloads, which can specifically target and kill cancer cells and promote tumour clearance.
However, many linker technologies — particularly those used in first-generation ADC bioconjugation like maleimide — have limitations, including inconsistent drug-to-antibody ratios (DAR) and unstable linkers. These can impact the safety and efficacy of the ADC. ThioBridge has been developed to overcome the limitations associated with traditional linker technologies.
Jai: Please can you give an overview as to why this technology is important for ADCs?
Campbell: Overcoming the shortfalls seen in ADC design over the last couple of decades is critical to improving a targeted approach to drug delivery, leading to a better therapeutic window with maximum efficacy and minimal safety issues.
ThioBridge is important for the advancement of ADCs as it addresses issues commonly associated with traditional bioconjugation technologies by:
- Creating a very stable and uniform DAR composition.
- Improving manufacturing efficiency through a high-yielding ADC platform with up to 80% single DAR species.
- Exhibiting a high degree of stability in serum and being less prone to losing its payload in the body before it gets to its target.
- Allowing for an extensive range of linker designs to optimize the stability, loading and function of the payload.
- Providing versatility in the range of different payloads with different functions that can be attached to antibodies.
Although one solution does not always fit all when it comes to ADCs, ThioBridge offers a versatility that broadens the options for design, improving the prospects of better treatments for patients.
Jai: Can you provide any examples of how customers have used ThioBridge in their projects?
Campbell: Our team at Abzena is made up of experts across all bioconjugation and linker technologies. When helping customers design and select the best ADC candidate, ThioBridge will often be included as an option within a matrix evaluation program. This gives the customer the highest potential to develop an ADC that fits the desired properties, and is stable and potent while also providing a clear intellectual property path with options to minimise or avoid license requirements.
ThioBridge is currently being used to treat solid tumours in Phase II clinical development, with another customer just about to start dosing cancer patients, and a third very close to an IND application. Many other customers are in early-stage development, evaluating ThioBridge with their payload antibody combinations to select a lead candidate for manufacture and clinical testing.
Jai: Can you explain how the ThioBridge technology benefits Abzena?
Campbell: ThioBridge is an Abzena platform technology designed to solve our customers’ ADC needs with precise control over drug loading and attachment sites to support efficient production and profiling.
The ThioBridge platform is a demonstration of our team’s ability to address the challenges of ADC design, development, and manufacture with creative solutions. In overcoming these difficulties, the platform allows us to support the delivery of innovative medicines to the patients who need them. In turn, the success of these therapies also helps further establish Abzena as an expert in the space, providing customers with solutions that may not be available elsewhere.
As a consequence, the ThioBridge platform brings sales and consequently revenue to Abzena that is used to develop our capabilities and generate new solutions to allow the team to better serve customers and advance the ADC field.