RE: Daiichi10 Sep 2024 23:05
P3
Now… Back to Avacta. In my view, AVA6103 – to be presented next month at a specialised cancer conference – is likely to be a PDC, similar to AVA6000, but with one of the following warheads (instead of doxorubicin):
i) irinotecan
ii) topotecan
iii) SN-38
iv) deruxtecan
Over the past several months management has made a big deal of the new (soon-to-be revealed) pipeline being very exciting (comprised of novel, highly potent molecules; boasting a range of modalities, etc.).
Moreover, management has seemingly shelved AVA3996, that was hitherto the first drug after AVA6000 in the pipeline, and which used another conventional chemotherapy, bortezomib, as its warhead.
Resultantly, my view is that AVA6103 will likely be a PDC containing the more novel SN-38 or deruxtecan, rather than the first-generation TOP1 inhibitors, irinotecan and topotecan.
If it’s SN-38, I believe that Avacta could be the sole owner of AVA6103. SN-38 is only under patent (held by Gilead) as part of the whole ADC molecule, Trodelvy. As it’s derived from irinotecan, a generic drug, so SN-38 itself could be used off-patent. When combined with pre | CISION, however, it could/would be patented by Avacta as sole inventor/owner.
If it’s deruxtecan, then Avacta would have to have entered into some sort of partnership with Daiichi Sankyo (and possibly AstraZeneca). Consider this: in 2019 when the Enhurtu collaboration was formed, Astra paid Daiichi $1.35bn upfront, and committed to up to a further $5.55bn in contingent payments. And that was only for a 50% share of future sales in most markets. Enhertu was in multiple pivotal trials at the time of the deal, but hadn’t secured marketing approval from any governing body.
In 2020, the second collaboration between the two over Dato-DXd – which hadn’t even commenced clinical trials at the time – involved similar figures. In return for a 50% revenue share across most markets, Astra paid Daiichi $1bn upfront, and committed to up to a further $4bn in contingent payments.
……
Whether its SN-38 or deruxtecan, the key point is that through AVA6103, Avacta will at last be going tête-à-tête with the leading ADCs on the market. With the largest of the ADC players – Pfizer, Roche, Daiichi / AstraZeneca, Gilead.
Then it’s down to which is a more targeted delivery platform, and accordingly which can result in greater amount of active warhead reaching cancer cells before dose limiting toxicities are hit.
However, there is also an important second matter to consider: cost. Avacta’s TOP1 inhibitor-based PDC would not include a monoclonal antibody component, in contrast to the TOP1 inhibitor-based ADCs of Daiichi / Astra and Gilead. Earlier this year, the National Institute for Health and Care Excellence (‘NICE’) rejected Enhertu for use on the NHS in England, following a failure to agree a cost effective price with Daiichi and Astra.
PDCs should be substantially cheaper t
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