RE: Time for talk is over26 Sep 2024 22:05
WAG
'The truly big money is in the pipeline for the Pre|CISION platform that allows more toxic warheads to be delivered to the tme and the pipeline is essential for showcasing that opportunity.'
Indeed, as explained in depth in the R&D Spotlight Episode 5.
Partial transcript follows for those wishing to word search the nature of disruptive technology in this interview:
https://avacta.wistia.com/medias/w78dwgqnaq
6:33 Francis Wilson:
So with AVA6000 we attached the FAP cleavage sequence directly to the molecule and we were able to do that fortunately because it fits, and because Doxorubicin interacts appropriately with FAP to give us the affinity we want, but not all payloads do that.
So what we’ve developed is an understanding both of the chemistry we can use to link via a linker to the payloads and then secondly how that linker itself interacts with FAP. So we can use the linker both chemically to join the two bits together, but also to adjust the level of FAP interaction so depending on whether you want a rapid release or whether you want to slow that release down. Then thirdly we really understand how, dependent on the nature of the payload, that effects the overall properties of the molecule and then we can use the capping group to adjust the fine overall properties of the molecule, so if you want to slow the release of the compound we can put in moeity’s that will increase protein binding for example, and what that does is to slow the rate at which the body excretes the overall drug and that means the drug is around for longer and gives us a greater chance to keep the molecule in the microenvironment, ready to be cleaved by FAP.
CC: So you can almost dial in the profile you want to vary payloads or Warheads.
Francis: Exactly. Dependent on the nature of the payload how quickly the payload itself is cleared. With Dox the payload is cleared quite slowly, so you don’t need to keep it there longer in the form of AVA6000. With other payloads that clear faster, you want the intact molecule to hang around longer to give FAP a chance to cleave it time after time.
CC: And then to the favourite part of the favourite slide, essentially then the third generation where we’ve got a whole new way of using the precision platform. Curtis tell us more about the third generation of our molecules.
Curtis: With this third generation we can completely change the delivery of the warhead with this method. So a warhead that would have a short half life and higher Cmax can be completely transformed, to achieve a compound that results in higher tumor concentrations.
Very little systemic circulation once you attach it to a biologic.
So using this approach the possibilities really are endless.
CC: So we can make an ADC, an Affimer DC (AffDC) we can even link it to a non-specific biologic like a DFC portion and completely change the profile.
Avacta has secured or is in process of securing IP over the above.
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