Avacta Group plc, the developer of Affimer biotherapeutics and research reagents, has announced positive results from the first preclinical in-vivo studies of its therapeutic Affimer molecules. The results meaningfully de-risk the development of the technology as a therapeutic platform; demonstrating that Affimer molecules possess good drug-like properties in terms of efficacy, serum half-life and tolerability.
Two parallel in-vivo pre-clinical studies have been completed. The first, a pharmacokinetics study looking at both human and mouse PD-L1 Affimer inhibitors engineered as Fc fusions, showed that Affimer molecules have good in-vivo serum half-lives and are well tolerated at the clinically relevant doses used in the study.
The second was an efficacy study using a mouse PD-L1 specific Affimer molecule in a syngeneic tumour model. In this study the Affimer PD-L1 inhibitor produced a statistically significant reduction in tumour growth demonstrating the bioavailability and functionality of the Affimer molecule in tumours in-vivo. No adverse effects were observed.
Alastair Smith, Avacta Group chief executive commented: “These results demonstrate that Affimer molecules possess good in-vivo drug-like properties in terms of efficacy, serum half-life and tolerability which is a hugely important milestone in the development and de-risking of the technology as a therapeutic platform. From the initial screening process for the Affimer binders we have been able to rapidly progress to evaluating them in in-vivo models, highlighting another major advantage of the technology. We are very encouraged by these initial positive results and will continue to focus on developing both our internal and partnered therapeutic programs towards clinical validation.”
PD-L1 (Programmed Death-Ligand 1) is part of the ‘immune checkpoint’ (ICs) target family. The normal function of ICs is to help to regulate the immune system and to prevent its over-activation towards healthy cells. Tumour cells often can take advantage of this system to “switch-off” and evade the immune system. By specifically targeting certain proteins involved with these pathways, it is possible to reactivate the patients’ own immune system and so destroy the cancer cell.
Fc (fragment crystallisable region of an antibody) fusions are a well-established approach to artificially extend the in vivo serum half-life of small therapeutic protein scaffolds. The Affimer biotherapeutic is genetically fused to the Fc region, replacing the normally larger antigen binding arms usually found in the antibody. In this way the Affimer biotherapeutic Fc fusion is maintained in the circulation by being captured and recycled back into the bloodstream in a similar manor to an antibody.
A syngeneic tumour model uses tumour tissues derived from the same strain of mouse as that being used to run the disease model. In this case, cancerous mouse cells (CT26 cell line derived from BALB/c mice) were implanted into healthy BALB/c mice to create the cancer model. This allows the pre-clinical efficacy evaluation of cancer immunotherapeutic leads, including immune checkpoint inhibitors and cancer vaccines, to be evaluated.