Member Info for BuenaVista

Hmm. Have you ever heard a CEO say or a company put in its promotional blurb "We're going to be a bit part player in this industry's future"?

Get real. It's called aspirations (and self-promotion).

Original patent with Priority Data: 61/528,824, 30.08.2011 (US)

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2013033396&_cid=P11-LELRPV-57617-1

Rather than those two links, the front page of the patent: https://patentscope.wipo.int/search/en/detail.jsf?docId=US307573390&_cid=P11-LELR81-54400-1

https://patentscope.wipo.int/search/en/detail.jsf?docId=US307573390&_cid=P11-LELR81-54400-1

Synthesis: https://patentscope.wipo.int/search/docs2/nat/US307573390/pic/O3GZdlxcgApjwXhKUiwlDVdH51qhwhgM-4Wc7ID4VwKENVbPvu9ZatBwtjwS27drMJKv7rKzq8OW7TVt3h_XiCg_HoBqAApkl0LPZsdI6Edu1Nmz1-AYVJeqkOYuCt1PzIxA1SM9-crpZMhMzH1YdcR1Vzq64QJq2K2JADW017MCSSNS1UqMv3uOPf1OgU6l?docId=id00000110464196

No, you've got that wrong as well! :))

"Why did #AVCT biopsy colorectal liver metastasis…?

"Interestingly, you’ll recall this is *exactly* what the pre-clinical PDX model was… colorectal liver metastasis…"

...and slide 84 for those who are blocked.

If the trial drug is shown to be clearly superior to the standard of care therapy then patients will be switched. This is normal ethical practice.

That could be the title of Jacqui Thornton's Avacta article!

I have everything crossed that C5 is being held up because they want to do weekly dosing as well in Phase 1a and that, if they can do that, a weekly dosing AVA6000 arm could be added to Phase 1b with a schedule to match the doxorubicin arm, possibly going beyond the 18 weeks that that would run for. That would allow for an early termination of Phase 1b at 18 weeks as proven that weekly AVA6000 is superior to 3 weekly doxorubicin - and we'd save 36 weeks of development time.

To reach the desired number of STS patients if STS is (compartively) rare... Will these patients be required to be anthracycline naive?

Fat fingers!

Jacqui Thornton

Freelance writer for the BMJ, Lancet, Nature and more, including newspapers.

https://jacquithornton.com/
https://www.linkedin.com/in/jacquithornton/

I wonder whether we'll get a write-up somewhere.

I haven't looked but I instinctively feel that the cash needed to carry out trials with 60 patients at "20 US & European Investigator Sites" will far exceed the income generated by Launch plus any milestone payments from partners ...UNLESS... there is financial assistance from the FDA's ODD and Breakthrough/Fast-Track, and the MHRA and EMA if application is made there for their orphan drug, fast track programmes.

" Assume P1a finishes in October, that’s June/July 2024 to complete P1b. They can’t afford it. "

If Phase 1b truly will be 12 to 18 cycles of AVA6000 given every 3 weeks that would be 36 to 54 weeks, as stated on slide 85, so an October 2023 finish for Phase 1a (which allows some slippage from end of Q2) would mean Phase 1b plus analysis completing some time between July and December 2024. Even more expensive.

Just across the road in Scale Space
Well understood by Neil Bell
Presence in the US (Maryland)
GMP manufacturing facility in Stevenage
NASDAQ-listed and 'cheap' if Avacta get licence monies
Experienced in NASDAQ fund raising
Experienced in clinical development in the US
CAR-T technology with their own IP
Could use Affimers instead of anitbodies
What's not to like?

I know, it's a crap poem.

Short of a buyout, Avacta need to license out the rest of the pre|CISION pipeline asap if those candidates are going to get to market with any patent life left in them.

AVA6000 and AVA3996 have both been studied since at least as far back as 2014.
https://grantome.com/grant/NIH/R42-CA156930-02

According to current plans, AVA6000 won't finish Phase 1b until late next year and AVA3996, a NCE and hence requiring full safety, tolerability and efficacy studies, will start Phase 1 next year. This is how long drug development takes. Patent life is until June 2035.

The rest of the pipeline needs an early patent priority date if they are straight prodrugs otherwise their patentability will have been invalidated by the 'non obvious' criterion, so their useful patent life is limited if they have yet to undergo their preclinical studies, although those could be shortened if either AVA6000's or AVA3996's leaving group is used. If different leaving groups are used then they will have to undergo full study. The pipeline candidates that are not straight prodrugs but prodrugs of analogues will need all the above plus full safety, tolerability and efficacy studies as they would be NCEs. In short, a lot of work to do, and a lot of cost as well, for Avacta to push all the pipeline through development whilst the patent life clock is ticking down to generic. Too much work, but not for several different well-resources majors. Of course it was always Avacta's intention to license out the pipeline. It's just that they better get it done very much sooner before the candidates become wasting assets.

That's a crap p poem

Not sure whether 'dox' in biopsy and plasma is just doxorubin or whether it includes doxorubicin's metabolites, which are less cytotoxic than doxorubicin itself and will be dispersed from the TME into plasma and then eliminated, in urine I suppose.

Well the doxorubicin in plasma will have been cleaved off AVA6000 by FAP, so predominantly by FAP in the TME. I guess doxorubicin in plasma has leaked there from a FAP site and is acting like standard infused doxorubicin - seeking out DNA to interfere with. Beyond that, how good this is will depend on the PK data and the rates of conversion/metabolism, distribution and elimination but I'd suggest that, as everyone associated with Avacta is happy, it is very good!

If I understand correctly, Phase 1b is now proposed to be 3 arms, one with doxorubicin and two with AVA6000 at different dose levels but every 3 weeks for 12 to 18 cycles. That will be 36 to 54 weeks! Plus set up and finishing off time. And then on to Phase 2. Just shows how long and slow clinical development can be. I wonder whether that is with Breakthrough/Fast-Track considerations or whether those FDA schemes will reduce the length of Phase 1b trial needed.

They are clearly happy with data from just two cycles for Phase 1a so maybe that part is not being redesigned to increase the maximum lifetime cumulative dose of doxorubicin. Or maybe it is and that's why we've not heard about DE4/C5. The MLCD would definitely need to be increased to do 12 to 18 cycles of AVA6000 - unless they're going for a low dosage (say 30 or 40mg/m²) for RP2D - as yet undecided. Maybe they're waiting for approval to do the proposed Phase 1b, which is certainly changed from the original, before embarking on further dose escalations. Must say I'm rather disappointed that they are sticking with 3 week cycles as that extends the Phase 1b time considerably compared to weekly cycles with minimal side-effects, but they know best what will work in the longrun.