Avacta Group and cancer drug developer ADC Therapeutics SA have entered into a collaboration agreement.

The partnership – financial terms of which were not made public – will develop drugs combining ADC Therapeutics’ pyrrolobenzodiazepine-based cytotoxic warheads with Avacta’s Affimer targeting platform.

ADC Therapeutics will cover all Avacta’s costs during the project. The firm also has the right to obtain exclusive licenses to the Affimer proteins for clinical development and commercialization.

Matt Vincent, Avacta’s VP of Therapeutics Business Development, told us: “The license ADC Therapeutics has from Medimmune for the PBD-based drug conjugates includes the ability to use that toxin with a certain number of antibodies and a certain number of non-antibody targeting moieties.

“Through our meetings and diligence with ADC Therapeutics, I believe the Affimer platform was selected because of multiple factors: the speed with which we can generate human Affimers to designated targets in order to begin animal testing; the flexibility in formatting, such as to utilize serum half-life extension techniques different from antibodies so as to avoid Fc-mediated recycling that may cause off-target toxin release or to create multispecifics; and tumor penetration characteristics that can be fine-tuned with the Affimer platform.”

Targeting tech

Affimers are small proteins that target and bind molecules on cellular surfaces in a manner analogous to monoclonal antibodies.

The key difference is that affimers are optimized to enhance their structural stability. They are also more resistant than mAbs to changes in environmental pH and temperature.

In addition, affimers are also easier and cheaper to manufacture than mAbs. Their small size means they can be produced in large quantities in modified cell lines.

Dr Vincent told us: “Affimer-based biologics can be less expensive and with less complicated manufacturing requirements when compared to antibodies.”

He explained that, “Production of therapeutic antibodies is generally highly optimized, but because of the limitations of the antibody structure – two different chains with multiple disulphide bonds and post-translational modifications – still can be expensive and time consuming in manufacture for use in human patients.

“In contrast, amongst the various formats we use for Affimer therapeutics, including those likely to be considered by ADC Therapeutics, the product is generally a single chain protein which reduces the complication of production.”

Vincent added that “in the context of drug conjugates, we also think the relative stability of Affimers in organic solvents permits a higher yield of drug conjugate as the existing coupling chemistries can be harsh enough to result in antibody loss and decreased percentage yields of final conjugate product from starting materials.”

Warhead

Pyrrolobenzodiazepines are a class of compounds that kill cells by binding their DNA and interfering with replication. In nature they are made by a group of bacteria known as actinomycetes.

Research suggests pyrrolobenzodiazepines could be a useful alternative to cytotoxic payloads such as calicheamycin, because they are not cross-resistant with other chemotherapy agents [1].

In addition, they have a unique mode of action sets them apart from the tubulin binders like maytansinoids and auristatins that currently dominate the antibody-drug conjugate arena.

Affimer tech

Avacta has already licensed the affimer technology to several other organisations, the first of which was Moderna Therapeutics in 2015.

And in January last year, Avacta agreed a deal with OncoSec Medical Incorporated, focused on gene therapies. A few months later the firm entered into a co-development partnership with Bach BioSciences.

More recently Avacta partnered with LG Chem Life Sciences, a division of the South Korean LG Group. The firm has since said the agreement could be worth up to $310 million.

References

[1] https://www.adcreview.com/pyrrolobenzodiazepine-pbd/