Anti-MMAE/MMAF payload antibody in PK study in ADC drug development

PKs are important in ADC drug development since it gives the understanding of the behavior in the body of the ADC, the antibody, the linker, and cytotoxic drug. In the case of ADCs employing monomethyl auristatin E (MMAE) or monomethyl auristatin F (MMAF) as the cytotoxic agents, ant- MMAE or ant- MMAF Abs can be of great value.

Talk with our expert for quote

• Validation Data
• Application
• Talk with our expert for quote
• Technical Resource

GeneMedi's GMP-Bios-Auristatin-Ab: Precision Binding with MMAE and MMAF-Based ADCs

As a result, GTU-Bios-Auristatin-Ab-01-2 expressed by GeneMedi has significant complementarity with ADCs containing MMAE or MMAF payloads due to its ability to bond with both. Conversely, GTU-Bios-Auristatin-Ab-02-2 provides selective acknowledgement to MMAE-based ADCs and has a lower impact on other targets. Moreover, out of the two, neither bounded with ADCs conjugated with DXD; such a move from GeneMedi aims at providing enhanced highly selective antibodies that offer ideal therapeutic performance.

Role of Anti-MMAE/MMAF Antibodies in PK Studies

1. Detection and Quantification:

   • Limitations in detecting the amount of MMAE/MMAF levels that circulate in the bloodstream or are released from an ADC are corrected by using Anti-Madden-ACA/MMAF antibodies. This is helpful in determining the stability of the ADC that has been formed, and the rate that the drug is being released.

2. Assessing ADC Integrity:

   • Using these antibodies, researchers can then assay the free MMAE/MMAF levels in circulation where an estimation of the linker stability can be deduced from. It might essentially mean that the free drug concentration is higher and the stability of the linker is lower, thereby promoting the release of the cytotoxic drug.

3. Safety and Efficacy Correlation:

   • Understanding the pharmacokinetics of MMAE/MMAF is also useful in determining the association between the concentration of the drug administered and the efficacy and toxicity. It is further assisted by the availability of specific Anti-MMAE/MMAF antibodies which enable measurement of the drug in various biological matrices with high accuracy.

4. Immunogenicity Testing:

   • Some ADCs can provoke immune response, resulting in existence of corresponding ADAs that could interfere with the drug’s efficacy and safety. As for the specific directions, it is possible to use the presence of Anti-MMAE/MMAF antibodies to distinguish between the drug per se and ADAs.

Application in ADC Drug Development

1. • Preclinical and Clinical Development: In the preclinical and clinical stages, Enzyme Linked Immunosorbent Assay or ELISA is employed to assess the drug’s partition, metabolism, and excretion with the help of anti-MMAE/MMAF antibodies. This information is critical in dosing regimen adjustment and the need to record the right dose that delivers the most therapeutic effect without harm.

   • Regulatory Compliance: Information obtained from such studies is indeed useful in meeting the regulatory needs of the drug by offering full profiles of how the drug is likely to behave in the body, which is vital for approval.

   • Formulation Optimization: Towards this end, PK studies help in obtaining valuable formualtion optimization data for the ADC. For example, if MMAE/MMAF releases before the desired time, adaptations to the linker structure or the antibodies can be made.

Anti-MMAE/MMAF antibodies are, therefore, essential for PK in the development of MMAE/MMAF-based ADCs as this means a comprehensive body of information that is highly influential in most courses of ADC drug development ranging from the basic research stage to the clinical stage.

Technical Resource

The Knowledge base of Antibody-drug Conjugate (ADC) The Landscape of ADC: Production, MOA, FDA approved-antibodies, and Functional assay What is antibody-drug conjugate (ADC)? Antibody-drug conjugate (ADC) in clinical application (Approved/BLA, phaseI/II/III) Main elements of antibody-drug conjugate (ADC): Antibodies and their targets Main elements of antibody-drug conjugate (ADC): Linker (structure and mechanism) Main elements of antibody-drug conjugate (ADC): Toxins/Payloads (Classification and function) Toxins/Payloads (Classification and function) of Microtubule destroying drug Toxins/Payloads (Classification and function) of DNA damage drugs Toxins/Payloads (Classification and function) of Innovative drugs Biological coupling technology Chemical based specific in situ antibody modification Endogenous coupling of amino acids and Disulfide re bridging strategy Glycan coupling Site specific biological coupling of engineered antibodies and Enzymatic method Biological coupling with engineered unnatural amino acids Review for ADC production, quality control and functional assay Product data of ADC