Developing antibody-like drugs targeting ion channels and GPCRs
Maxion Therapeutics was incorporated in April 2020 to capitalise on the therapeutic opportunities present by KnotBody technology, an innovative molecular fusion format invented at IONTAS.
Integral membrane proteins such as GPCRs and ion channels represent an important but challenging targets class. Ion channels in particular represent a relatively untapped class of targets for therapeutic intervention. Despite much effort and expenditure by pharmaceutical and biotechnology companies there has been few successes in the quest to generate potent and selective antibody inhibitors of ion channels.
In contrast, a multitude of venomous animals block ion channels using small cysteine-rich peptides in defence or predation. Although these naturally occurring “knottins” may at first glance seem promising as therapeutic agents, they suffer from manufacturing difficulties, short half-lives in vivo and a lack of specificity. KnotBody technology combines the benefits of nature’s “knottin scaffold” with the advantages of the antibody scaffold.
KnotBody®
technology
KnotBody® technology fuses venom-derived or venom-inspired cysteine-rich peptides into an antibody complementarity-determining region (CDR) retaining the folding and function of both molecules and thereby combining their benefits. The cysteine-rich peptide enjoys the extended half-life of an antibody molecule and the antibody gains additional diversity within a scaffold which is pre-disposed to blockade of ion channels.
The format is amenable to phage and mammalian display technology which facilitates further optimisation of potency, selectivity and developability by engineering both knottin and antibody loop sequences.
KnotBody®
benefits
- Benefit from millions years of toxin evolution for functional ion channel modulation
- Improved selectivity through concurrent engineering of antibody and knottin components
- Production and half-life characteristics of established antibody therapeutics
- One specificity on Knottin domain and one specificity on antibody domain
- Bi-valent and bi-specific within regular IgG tetramer format
Opportunity
Maxion Therapeutics, founded by John McCafferty (co-founder of Cambridge Antibody Technology and IONTAS), represents an investment and co-development opportunity generating antibody-like drugs to targets previously considered intractable.