The development of Antibody Drug Conjugates (ADC) using conventional intact antibodies has proven challenging with only five ADCs successfully approved to date but over 60 clinical stage failures [1]. A major problem with intact antibodies as an ADC platform is the limited therapeutic window. With conventional intact IgGs, safety and tolerability issues often arise which limit the total dose that can be safely administered.
Avibodies™ can rapidly and efficiently penetrate tumors. They durably persist within the tumor for weeks while clearing from the systemic circulation within hours. Avibodies can deliver highly potent payloads with far less toxicity. They can be reformatted from existing intact antibodies.
(1) JM Lambert and CQ Morris, Adv Ther (2017) 34:1015–1035.
Avibodies consist of the key target binding domains of intact antibodies but in a compact format.
Avipep utilises proprietary conjugation sites on the Avibody surface which results in an exact Drug-Antibody Ratio (DAR) of two or four drugs per Avibody. This supersedes random conjugation which produces poor quality heterogeneous products with variable (DAR).
A Phase I clinical biodistribution trial using 124I-PEG-AVP04 and Positron-Emission Tomography (PET) imaging in prostate and ovarian cancer patients demonstrated excellent tumor uptake with no uptake in normal tissues. Rapid targeting of the tumor was observed in 24 hrs with high tumor load extending to over one week. The trial met all safety endpoints with no adverse events nor immunogenicity. Metastatic lesions in lymph nodes and liver were clearly identified and with clearance T½ beta ~ 44hrs the PEG-AVP04 demonstrated improved pharmacokinetics (PK) compared to intact antibodies.
The most notable results from the study include:
Taken together, these data demonstrate that Avibodies achieve a superior level of payload delivery to tumors which should translate into higher therapeutic efficacy, lower systemic toxicity and a greater therapeutic window when employed as Antibody drug conjugates (ADCs).