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I think they've ceased calling it 1a or 1b and are just going with Phase 1 as they are doing both dose escalation and dose expansion at the same time, with the expansion being for any dose level (any cohort) where therapeutic benefit is being shown.

Comms is very poor and causing all the problems I listed earlier.

And King Charles was travelling to New York for that fortnightly pump.🙄

The relevant part of my communication, without the formatting that makes email a lot easier to read than this site's formatting:

RNS of 13 Dec: "Cohort 7, the final cohort in the three-weekly dose escalation safety study of AVA6000, has completed enrolment and is ongoing." and "A maximum tolerated dose has not been reached in the three-weekly dose escalation study despite dosing approximately 3.5x the normal level of doxorubicin in the highest and final dose cohort in this part of the Phase 1a study."

Does this mean that an MTD has not been reached according to the Phase 1a dose escalation protocol, although the patients continue to be treated in order to understand long-term tolerance and for study of the efficacious benefit they are receiving, in which case was that sentence in the RNS in lieu of an official SDMC sign-off? Or does it mean that no MTD has been reached *yet* and sign-off by the SDMC hasn't occurred and will be RNS'ed when it does happen?

[In line response from AS:]

An MTD has not been reached which is a conclusion of the SDMC ie safety for this level of dosing has been confirmed and signed off. Patients continue to be treated because we continue to treat them, as we are doing in many of the earlier cohorts, until progression.

RNS of 13th December: "A maximum tolerated dose has not been reached in the three-weekly dose escalation study despite dosing approximately 3.5x the normal level of doxorubicin in the highest and final dose cohort in this part of the Phase 1a study."

I agree, not that C7 having finished with no MTD should have been RNS'ed, but that it should have been made clear in that RNS that that was the case. Comms are clearly not being thought through and it causes uncertainty for investors, opportunities for FUDsters and wastes AS's time on what should be unnecessary personal communications.

I have a solution to this for AS - give the draft RNS to the office junior and ask the simple question: "What does this mean and what's the status of it all?"

"C7 must be very close to finishing"

C7 as a dose escalation cohort has formally finished and been signed off as no MTD found (personal communication from AS).

Dosing of progression-free patients in C7 continues, as for previous cohorts (again, personal communication from AS). Efficacy and continuing PK and PD data from these cohorts is obviously open-ended until such time as the last patient comes off treatment, for whatever reason.

So I think they will have the Phase 1a Arm 1 safety, tolerability, PK and PD all ready for AACR as a data package in its entirety, plus whatever narrative with caveats they can put together about efficacy.

It hasn't. It's just reached its target buy in price and is starting to pump.

Ignore Timster Rob. You made a valid point. The regulatory hurdles for getting a new razor on the market are notoriously high.

AHS, if you don't understand the biopharma industry then you'd do best to wait until there is revenue or commitment from a big player, or stick with IT and prospector companies.

Ah. I see. You're an accountant AHS.

Unable to reply to 13thmonkey then AHS?

For someone not invested eggy is very "knowledgeable" about the company's internal goings on.

VR, if you think the trial could fail would you care to elucidate how it might fail? No, of course you wouldn't date. But maybe give it a try... Give us a laff.

Thank you D-G. It is, as I thought, very different from the UK.

Do patients on a clinical trial in the US have to pay for their medical care does anyone know? It's normal I think for patients with medical cover to have regular checkups at which time cancer could be picked up but those without medical cover present later with developed conditions.

Have you ever freewheeled on a bike HurstBot?

Sorry to hear that about your friend Bella. The immune system is very complex with positive and negative feedback mechanisims.

You're welcome.

@Thompi, to answer your question:

Over a 6 week period, Arm 2 patients get 3 doses, so the total given over those 6 weeks are 3x160, 3x200, etc, which is 480, 600, etc. If these amounts were administered 3-weekly, as in Arm 1, over 6 weeks the doses would be 2x240, 2x300, etc.

At the highest Arm 2 dose of 310 (3x310=930 over 6 weeks), the equivalent given 3-weekly would be 465 (2x465=930). Whilst a dosage of 465 would be outside the range of the Arm 1 study, this high dose can be achieved by giving 310 every 2 weeks and 310 is well within the range of the Arm 1 study (i.e. no MTD).

Of course, dosing every 2 weeks rather than every 3 weeks gives the body's healthy tissues less time to recover so any changes to the side effects profile will be monitored closely (degradation of the immune system, near permanent mouth ulcers, nausea, etc) as well as efficacy against tumours. Drug development is always risk vs benefit, finding the therapeutic window.

Well, you know, at the start of a project, when everything is new, the timelines are very much finger in the air estimates. However as the project progresses, and experience of the environment is gained, one might expect the predicted timelines to be tightened up. In short, my concern: estimates of timelines don't seem to have improved with experience.

C7 has completed as far as the SDMC is concerned - no MTD found. Although this was not explicitly stated (no mention of the SDMC), it was inferred in the 13 Dec RNS. Dosing continues, as in previous cohorts, for patients whose disease has not progressed. The 3-weekly study is all done and dusted, just efficacy and, I guess side effects, data being collected now.

As the 160 dose has already passed the safety and tolerability test in the 3-weekly study, there is no need to dose one patient first, so three patients can be dosed at the same time (or staggered, as they pass screening?) and the start of cohort RNS will be released when those 3 have all been dosed.

The planned Arm 2 dosing levels are 160, 200, 250 and 310. Their equivalents on a 3-weekly study (i.e. same amount after 6 weeks) are 240, 300, 375 and 465. C7 was at 385 with nio MTD, so all Arm 2 cohorts should be good for this simpler dosing regimen all the way.

What concerns me about the stated timeline for Arm 2 of completion by end of H1 is that if it takes even 2 months to recruit patients for the first cohort, and it could be 3 months, then if that rate of recruitment continues only 2 or 3 cohorts would be possible by the end of H1, assuming no problems halting the study early, and that would mean another deadline overrun, possibly to end of Q3, and that would be another example of overpromising. Anyway, time will tell.