Member Info for BuenaVista

It's a safety and tolerability trial looking for improved efficacy...

As all the dose levels in Arm 2 have been passed safe by the SDMC for the 3-weekly trial, the difference here with Arm 2 is that it will be announced when the 3rd patient in each cohort has been dosed compared to the 1st patient in Arm 1. That means it is possible to project when the cohort will finish and be assessed, as we saw in the RNS with the 'date' of "by the end of April". That, of course, assumes no DLTs, deaths or withdrawals causing delays.

The 3rd patient would have been dosed in the US yesterday (probably). Two weeks till the next dosing and two weeks for observation takes us through to 17 April. Then time for the SDMC to assess the data... Surely that could be done in much less than the 13 remaining days in April? Given, you know, 28 February's anticipated "read out of two-weekly and three-weekly dose escalation study data in late Q2 2024" and the statement today that "Avacta remains on track to begin the dose expansion efficacy study in the second half of 2024."

@Timster, doxorubicin could be used as is because it has a free amino (-NH2) group that can be bonded to the R-D-Ala-L-Pro- dipeptide. Whereas brtezomib (Velcade) couldn't be used as is because it lacks that free, or any, amino group so a version that has that free amino group had to be designed (by Bachovchin's team).

The presence of an amino group is a decider for any prospective warheads.

I fear that that is my reading as well. However, it is a given as there is only one trial (Phase1aA2) so it seems superfluous to state it.

GeneralOz - desperate and totally irrelevant attempt at FUD, I suggest you close your short asap.

Thorn - doxorubicin is easy to do, and (and this may come as a surprise to you) Avacta don't have any 'more potent warheads' in their store cupboard; it will be for pharma companies to use their own more potent warheads when they licensed the platform.

@PL, point taken about the length of C1, but what does "in parallel" mean? Sites or cohorts? That is ambiguous and needs clarification.

There clearly was a problem recruiting patients in the US. Glad they've extended the trial to the UK.

McGurk is lying. This RNS does not extend the timelines.

Or did I get that wrong and the several orphan indications is intended for the dose expansion (Phase 1b) study?

Does "in parallel" mean dosing in the US and UK in parallel or dosing cohorts in parallel? There's no mention of further cohort though.

Are we back to a single orphan but now unspecified indication for Phase 2?

"The combined data from the three-weekly and two-weekly studies will provide information to allow the Company to define the dose and schedule to be used in future efficacy studies. Patients can be dosed in parallel in the two-weekly dose escalation study and Avacta remains on track to begin the dose expansion efficacy study in the second half of 2024. The data from the expansion study will be used to inform the optimal choice of a single orphan indication for the Phase 2 efficacy study which will follow on immediately."

Let's dissect this and see what it really means.

"Investing in this company should be all about the science." The science and the management. Science very good, management very meh.

"I don’t think that anyone on here is questioning the marvellous results (similar to rat trials) that Avacta have announced for 4 out of 40 patients. Neither the safety profile achieved. But 4 is not statistically significant."

Duh.

Phase 1 is not supposed to provide statistically significant efficacy. That is the first thing to be understood.

The second thing is that the cancer types included in the Phase 1a Arm 1 study were chosen to prove the platform, not to gauge efficacy.

Well people can look at the history, the current situation and the timelines and make up their own mnds, for both clinical development and funding.

Fusion: one in Phase 2, two in Phase 1, two in pre-clinical

Avacta: -------------------- one in Phase 1, two in pre-clinical

Quite dissimilar

https://fusionpharma.com/fusion-pipeline/

@B2HS2L, these are the long-term secondary outcome measurements from the trial protocol (definitions standard for all oncology trials):

6. Duration of Response (DoR) [ Time Frame: Up to one year ] DoR is defined as the duration of time from date of first response to date of disease progression, as per RECIST v1.1

7. Progression-free-survival (PFS) [ Time Frame: Up to one year ] PFS is defined as the time from the date of the first dose to the date of the first documentation of confirmed disease progression or death, whichever occurs first, as per RECIST v1.1

8. Overall survival (OS) [ Time Frame: Up to one year ] Overall survival (OS), defined as the date of first dose to the occurrence of death from any cause

@gje306, I have an ongoing project to fly to Mars.

So the answer to your question is 'no'' - just screening (making preparations) is enough to call the study 'ongoing'.

It is patently NOT the case that there is a delay of months between screening and starting AVA6000 dosing. Just take a second to think about that.

The trial will take patients with metastatic cancers - so late diagnosis. In the US, these are likely mostly people without health insurance and/or the ability to pay the cost of their hospital stay - people who can't afford to visit a doctor. I emailed AS asking whether a backup application had been made to the MHRA in order to be able to also carry out the study in the UK, where the catchment area for the 5 sites used in Arm 1 is much larger than that of the 2 US sites. No response as yet.

The delay in starting to dose the patients needs explaining - another thing that requires clarity from AS.

Lucky he could do a healey so quickly.