Member Info for jive_turkey

This shows the difference between a US listed company and one on AIM. Morphic were able to get enough money to not only bring their pathfinder drug to the clinic, but they had enough to start 4 (four!!!) Phase 2 studies with their drug. Imagine Avacta selecting four different cancer types for ava6k in the P2 study. Instead, we struggle to bring one, and even then the AIM traders constantly moan about dilution. Avacta raises pennies. It's just an entirely different attitude on the other side of the Atlantic.

@Timmy - I'm torn on this now. I've always considered it a positive that they can continue going to higher doses, even going beyond what they would reasonably use as the standard dose. But three years to finish a P1a is starting to get to me, so finishing at C3 may not be an entirely bad thing.

@BV - CC told a few individuals during the AGM that the 3rd patient in cohort 3 was due to be dosed that same day (i.e., the day of the AGM). Second hand info, of course, so make of it as you will.

@54 - that's exactly how the vote went last year. I think the basic idea is that it's not worth the time to sort through the details of number of shares owned, etc. Most of the measures pass with an overwhelming majority, so it's just a formality. So if most of the hands go up in the room, the measure passes. In addition, they will already also have tallied all the votes that were done before the AGM, i.e., big holdings and those that couldn't attend. So they basically already know the answer before the vote happens. If it is close, then there are probably other formal rules that they will follow.

@54 - Labour have no plans to change the ISA annual allowance or the maximum value allowed (i.e., none).

As anyone who has listened to CC's presentations over the last couple months (including yesterday) will know, she has put a huge amount of emphasis on the fact that they see a 2-log difference (i.e., 100x) between the concentration of dox in the tumour vs. in the plasma, the so called tumour-to-plasma ratio. While this sounds very impressive, I've been lacking a bit of enthusiasm for this, because we were never given a comparator. i.e., if standard dox was used what would this ratio be? Apparently this has never been published for straight dox.

This has been measured, however, for a number of ADCs. ADCs, as we know, are the bees knees in modern oncology treatment, because they allow specific targeting of a warhead to the tumour. Because they are more specific, much more cytotoxic warheads can be used. So what is the tumor-to-plasma ratio for ADCs at 24 hours?

T-DM1 (Trastuzumab Emtansine): In clinical studies involving T-DM1, a tumor-to-plasma concentration ratio of approximately 3:1 to 5:1 was observed within 24 hours after administration.

Brentuximab Vedotin (Adcetris): Another ADC, Brentuximab Vedotin, targeting CD30-positive lymphomas, has demonstrated tumor-to-plasma concentration ratios in a similar range, often around 4:1 to 8:1.

So, at least for these two ADCs, the ADC is around 3-8 times more concentrated in the tumour than in the blood. Ava6k blows this out of the f'ing water. 100 to 1 with Precision.

This is what Avacta are sitting on.

@AVCT - I don't know. My only guess is that they've decided to focus on much more toxic warheads, i.e., MMAE given how well Precision is working. But it would take a lot to make a company give up a on an asset at this stage to focus on another.

As stated by B2 though, hopefully they are able to sell this asset to that it isn't wasted.

Hey Ice. No, the 3 cohorts in the presentation was in the dose expansion phase (1b), not the dose escalation phase (1a - where we are now). The Q2W will likely have four cohorts or more (they said max 4, but i can see them going over this). The dose expansion phase 1b, will have up to 3 tumour types, so 3 cohorts.

B2 - did they say that at the AGM today. If so, excellent news!

We've now heard a few times about Avacta releasing an update of their pipeline in 2H24 (another reference was given today at the AGM). It's just been reported on Telegram (thanks Grant!) that CC said: "You guys are going to love the pipeline update later this year."

They are clearly building it up, so it's not going to be simply another chemo with Precision on it. And from the fact that we haven't heard anything about ava3996 for months, my guess is that this has been quietly shelved. Likely for a good reason.

So what could the big changes to the Pipeline be? And why can't they simply say it now? Why the build up?

From my side there seem to be two big things to report, both requiring partners (likely negotiations very advanced or already completed):

1) ava6k for one or two big indications, e.g., Breast, Lung or Ovarian. These would require expensive trials, so we would need a partner.

2) A modern toxin (e.g., MMAEs) combined with Precision. With the data so far, this seems inevitable. Avacta are short on money though, so we would likely need a partner for this. That's good, it time into clinical trials would be greatly reduced with a big partner.

3) This could be the big curveball, a Precision based ADC and Affirmer-DC.

4) an update on the Affimer programmes, which we saw the first data from last autumn. This looked positive, but at a much earlier stage than Precision. And since Precision is the bees-knees, I would have thought that that would be their focus.

Nope. Technically it is July 2nd.

I think it's safe to say that the Q2W patients will continue the treatment as long as they are seeing some benefits, just like we saw with the Q3W cohorts. They will only drop out if:

-disease progression, i.e., tumours continue to grow or spread.

-they need to drop out for health reasons. Due to the safety profile of ava6k, it would likely not be directly related to that, but rather to the cancer itself, or lingering effects of previous drugs.

-the reach the maximum cumulative dose. Unlikely for the Q2W patients.

-death

Other than that, they will continue to stay on drug and hopefully continue to see tumour shrinkage.

@cj - it's possible, but it's not clear if C2 could be complete and have the SMDC meet to give approval to move on to C3. But I could imagine, if this is the case, that it may be included in the RNS on Wed. morning.

@nursesteve - for clarity, the SMDC did review the data at the end of April and gave the thumbs up to dose the patients in cohort 2. So there was no delay, we weren't expecting to hear anything else.

Rambo's right though, they should have had two RNSs, IMO. The first with the SMDC thumbs up and the second when all three C2 patients were dosed.

Spot on gje. If Mr. 80% was on regular dox, he would have had to stop treatment last June or July. Statistically, he would be dead by now. But ava6k has let him continue for much longer and his tumours have continued to shrink. As has been pointed out, we are now in the window where he may be expected to show a complete response. Fingers crossed for him

As a side note, it is much too early for any of the Q2W patients to show a complete response yet. But I have little doubt that significant tumour shrinkage has been observed for Cohort 1, at least.

I looked at the Point Bio pipeline in December or January after the EL TO, and Canseek was still in the Discovery phase. I think they were waiting for P1 readout before deciding whether to commit to the pre-clinical studies.

@ES - I don't think that Point had even started Pre-clinical work on Canseek before they were bought out. So, even if it was a priority for EL it wouldn't move into clinic for another year or two. My guess is, unfortunately, that EL's focus will be on the more advanced products in Point's pipeline, getting them through the clinic, for the time being. That said, in doing their due diligence for the TO, I'm sure their scientists looked in detail at all their assets, and perhaps Canseek stood out, so maybe they will start Preclinical work in the near future.

That's Keytruda, the largest revenue producing drug ever. >$25B last year alone. It's very impressive but with some serious side effects too. In this study they had a 100% cure rate. However, they only allowed patients on the trial that had a particular genetic marker, and people with that genetic marker only make up about 15% of bowel cancer patients.

So it's a great treatment, but the headline oversells the results.

@AVCT - the financials are not my area of expertise, but from what I can gather, last year the AGM resolutions proposed up to ~£30M in shares, and this year it is £36M. Not too different (compare resolution 9 from both years).

https://avacta.com/wp-content/uploads/2023/06/23_0524-AGM-Notice-Notes-Explanatory.pdf

https://avacta.com/wp-content/uploads/2024/05/2024-AGM-Notice.pdf

Because it is the same resolution every year. Not just for Avacta but a bog standard listed company resolution. It's not that they will do it, it's just giving them the power to do it, if the BOD feels it's necessary.