Member Info for Mansa

Https://www.bbc.co.uk/news/articles/ce8p57y35lzo

ADC which extends OS from 12.8 to 16.5 months and PFS from 4.3 to 5.6 months.

'But crucially it improves quality of life. It has fewer side-effects, women are able to keep their hair and it is given by a drip every three weeks, instead of weekly with conventional chemotherapy.'

Prof Ruth Plummer, NHS national clinical lead for cancer drugs, said it was the "most significant breakthrough" in treating these hard-to-treat ovarian cancers "in over two decades" and added she was "delighted" it was available on the NHS.

But a little birdie told me the worlds only interested in treatments which CURE cancer, so not sure why the BBC is reporting on this lol.

Https://www.bbc.co.uk/news/articles/cy82l435171o

Oh look another cancer drug gaining attention, but doesn't CURE lmao

Regardless, SGC is already chemotherapy resistant (hence why anti-androgen therapy first line). So the outcome is the same, faridox is treating chemotherapy resistant patients regardless of whether they've had chemotherapy treatment or not

Its a PEPTIDE drug conjugate. Peptides/proteins have notoriously short half lives (which I'm sure the boffins had in mind when testing AVA6000, because any scientist would have known/anticipated this). Would be a problem if the peptide was the active drug. FAP has high baseline kcat/km. So its efficient at cleaving and releasing dox, even if AVA6000 half life is short. And as the active warhead is dox which has a long half life, unlike Exatecan, the kcat/km doesnt need to be modulated

Wrong. The half life of AVA6000 released dox has been reported at around 52 hours (a 40% increase compared to conventional dox). So how can you say that theres negligible dox in the tumor more than 90% of the time?

But the WARHEADS are different and have different PK properties.

From the latest R and D spotlight

'That works because we have this very, very specific cleavage site, releases doxorubicin, but we take advantage of doxorubicin's own very long PK. So we don't need to keep it in the tumor for a long while. In fact, it's better for us to clear it quickly.

The drug gets taken up into the tumor, and then it stays in the tumor.

The PK, the half life, it's actually four times as long. Important to note. '

Https://avacta.wistia.com/medias/8f6ompcjib

Around 3.50 mark onwards

In addition, released dox had a 40% lower volume of distribution and a >40% increase in plasma elimination half-life compared with conventional dox (75 mg/m2, historical data).

https://www.abstractsonline.com/pp8/#!/20273/presentation/10472

So Dox from AVA6000 has a longer half life compared to conventional Dox.

Dosing every two weeks would enable FAP-Dox dosing to align with other chemotherapy treatment schedules. For example, cyclophosphamide and epirubicin are both given fortnightly and are commonly administered in combination with doxorubicin.”

“Completion of the two-weekly dose phase of the trial demonstrated no difference in outcome or safety profile between the two-weekly and three-weekly dosing schedules. However, this single-agent data is important in partnering discussions as it is likely to increase interest from partners who may be interested in FAP-Dox as a combination treatment with an existing chemotherapy that has a two-weekly schedule.

https://x.com/RAH00084/status/1907315591020515648

Not sure what the source is

Https://www.bbc.co.uk/news/articles/c1d4n119xr7o

Https://avacta.com/research-development-spotlight-series-episode-5/

Explained around 8.19 mark how that doesn't really matter with dox in the form of AVA6000 compared to other payloads.

Touched upon this in todays presentation around 50 min mark.

It was not a correct interpretation of the CLINICAL data, if you understand anything about clinical trials and cancer therapeutics.

Https://avacta.com/christina-coughlin-aacr-2024-ava6000-data-presentation/

Mentioned here at around 22:00. I understand how a reduction in Cmax sustained across all dose levels will obviously translate into a better safety profile. Christina points out that there is a 'dwindling' in the percentage reduction of the AUC at higher AVA6000 levels, which means a 'longer exposure in the blood' and 'that combined with the reduction in Cmax is supporting the favourable safety profile.' Does a 'dwindling' in the percentage AUC reduction at higher AVA6000 doses not translate to lower tolerability regardless of Cmax?

Hi,

Can someone please explain the significance (if any significance) of the following: From todays video presentation of ESMO poster, the Cmax of AVA6000 released Doxirubicin compared to conventional Doxirubicin has been reduced as highlighted in the presentation (I understand the implications of this). However the AUC of the max AVA6000 dose is similar to conventional dose Doxirubicin?

The major benefit of participating in a phase 1 trial is the potential that the experimental therapy will shrink or stabilize the cancer.2 Overall, it is estimated that approximately 7% to 11% of patients experience tumor shrinkage in phase 1 trials, with up to 34% to 48% experiencing at least stabilization of their cancer.6,7 The actual response rate varies between trials. This may be particularly important to some patients, as most patients enrolled in phase 1 trials have metastatic disease that has already progressed after the receipt of other treatments.1 In addition, other potential benefits include access to new treatments and helping advance scientific research.

However, some experts caution that phase 1 trials offer little benefit to most patients, as the risks are typically more pronounced than the benefits in this early phase of experimentation.3,10 There is some debate on the ethics of phase 1 trials, and patients should be aware of all potential risks before agreeing to participate.

Https://www.ema.europa.eu/en/medicines/human/EPAR/caelyx-pegylated-liposomal

For metastatic breast cancer, in a study involving 509 women, Caelyx pegylated liposomal was as effective as standard doxorubicin: the time until the disease got worse was around 7.5 months in both groups. However, patients receiving Caelyx pegylated liposomal were less likely to have heart problems.

Liposomal formualtions of Dox such as Caelyx have been approved for certain indications on the basis of improvement of the side effect profile and not efficacy when compared to straight Dox.

'In a phase III trial, 509 women with MBC were randomised to pegylated liposomal doxorubicin (50 mg/m2 every 4 weeks) or doxorubicin (60 mg/m2 every 3 weeks). There was no significant difference between the two groups with respect to progression free survival (pegylated liposomal doxorubicin 6.9 months, doxorubicin 7.8 months; hazard ratio 1.00 [95% CI 0.82–1.22]) and overall survival (21 months versus 22 months; HR 0.94 [95% CI 0.74–1.19]). However, there was a greater risk of developing cardiotoxicity with doxorubicin treatment (p

Https://www.bbc.co.uk/news/articles/cl5k58x9g83o