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Could be AVCT.
@WAG - I think it is important to separate two types of discussions. 1) would be for ava6k, either for other indications (breast, ovarian) or for certain geographies and the 2) would be to get Precision to attach a bespoke warhead.
For the first type, indeed clear efficacy signals are needed. Although the data just presented last week (covering C1-C6 and part of C7), assuming the full dataset is available to interested parties, likely already has enough info to make an informed choice. As has been stated, the earlier a partner comes in the cheaper it will be for them, although with a bit more risk. So they have their own risk/valuation calculations to do. If they wait until the end of the 2nd arm of P1a, and the efficacy for STS (and maybe other indications) is very clear, then the valuation goes up significantly.
For the 2nd type, it's not clear exactly how much more info the second arm of P1a will bring. Yes, it will be more patients with extensive data (always good) and likely more biopsies, but how important that will be for the Precision mechanism in general isn't clear to me. For this type of deal, the PK data that is already in hand should already be enough to have a very good idea of how much of the new warhead will be released in the tumour and the likely effectiveness of this concentration (based on their previous studies).
As BV has said a few times, for any company seriously interested in Precision, one would expect them to have synthesised the new Precision+warhead drug (or worked with Avacta to do it) and done preliminary pre-clinical tests (potentially already with mice - not a full study mind you, but enough to see if there is reason to go ahead with the deal).
Given the massive testing market at the time when those statements were made, they was perfectly reasonable. There was a massive market opportunity for a high quality, British made LFT. It was reasonable to assume that the UK government would actually fast track validation and support British industry, instead we now know that they held it back. There was also no way of knowing that a new variant would come along (at least not that quickly) that would be significantly less deadly which effectively collapsed the market.
I, for one, say that the statements made by the company throughout 2021 were justifiable at the time that they were made and don't hold it against AS or the BOD. But the danger in going after a highly volatile market like testing during a pandemic was the uncertainty in how long the market was going to last. And from everything I read about the mutations and spread of corona, reality was on the very short end of the distribution of probabilities predicted by the experts. Good for the world, bad for testing companies.
Here is a transcript of what Dr. Tap said at the science day about standard dox and what Dr. Coughlin said last week about ava6k. (thanks to BMH on X for posting the videos - https://twitter.com/BMHLTD/status/1736326494035603668).
Dr. Tap: "[For standard dox], most likely we don't see remissions, remission means that we see the tumour melting away. We can often see responses, but meaningful responses are only in 15-20% of patients. I'd love to see that increase. That can help with palliation, that can help with surgical conversion. But sarcoma is really a disease that we need to continue to treat. So having a drug that we can use for a long periods of time is what then translates into improved overall outcomes, like overall survival. And this also comes into the quality of life aspect where if you are giving a patient a drug that is not affecting their quality of life for the long term. That becomes really important."
"[For standard dox] median progression free survival (PFS) in a first line setting is 6 months and overall survival is 19 months and the overall response rate is 18%. I highlight this because sarcomas are diseases that don't always shrink when we treat them. So I don't always look at the RECIST response rate [how much tumours have shrunk], we look for stability, [stopping them from growing] and that's what is meaningful for patients. So we need to think about that when we interpret data. But I also want to point out the median number of cycles was just 4.2 months, which is hitting that limit of 6 [allowed] cycles. And median PFS is only just a few months after that. Why? Because when you stop the drug [dox] patients progress. That is one of the major limitations of doxorubicin, that we can only give it for 6 cycles."
Dr. Coughlin last week:
Dox is limited to 6 cycles (or 18 weeks, 4.5 months) and that is because of the cumulative toxicity. So the benefit that we have here with ava6k is not just that we are shrinking tumours but those tumours are shrinking and staying in that shrinkage, we're stabilising the disease for a prolonged period of time that just can't be achieved with dox. And that's right there with that favourable safety profile. So the patients have strong disease stabilisation, responses that last for time, and they are not experiencing the really problematic toxicities that are associated with dox."
It's almost as if Avacta have cracked it....
@oftinhope - indeed, especially for tumours like STS, the goal is to keep their growth in check. This was highlighted by Dr. Tap back in the science day presentation and by CC in the presentation last week. So instead of surviving for ~12 months (including 4-5 months of being terribly sick due to the chemo) when treated with standard dox, the patient may survive 24-36 months and have a much higher quality of life (low side effects). Also, for many patients, they can only have surgery if the tumours are below a certain size threshold. So shrinking them can be extremely beneficial.
Thanks Estura...damn. ;)
JP Morgan Healthcare conference would be the best, but that's already in January, so it may be too early (as a side note, a company i follow just announced that they will have an oral presentation there, so the schedule is made...but not made public, it's up to the companies to announce if they have talks/posters). The next biggy is the AACR in April...which could be excellent timing.
‘why wasn’t this released at the same time as the data?’.
Because these are two separate and unrelated events.
Hi @Energy - it would be very unorthodox for a publicly listed company to obtain new funds from a venture capitalist. At this stage of Avacta's development, it would be much more common, and make more sense, to sell equity to a large investment fund or a major pharma company. While this would end up diluting the share, it can have a very positive effect on the share price, given the confidence in the company that would result. I would hope that the board, including Shaun Chilton, would be looking into this option, on top of licensing, in detail at this stage.
Well said @DTW!
@A1 - as Energyshares found for us, for trial changes formal approval isn't given. Avacta submit the changes and the FDA have 28 days to respond if they do not agree with the changes. So I expect to hear once the first patient is dosed in the bi-weekly study.
Note that one of the benefits of ODD status is that the company are in close contact with the FDA, so it is near certain that the FDA was involved in the design and pivot towards the bi-weekly study.
As Timster says, this is already approved and going forward, as they are already screening patients.
@RD - just for correction, there was no product launch that was cancelled last summer. Nor was there a widely expected Dx update. All that happened was that the company presented 5 or 6 posters related to Tx and Dx at the AGM. The Dx poster on a new affimers based product had information that had not been fully patented yet, so they didn't show the poster. That's it.
We were told that the product (I believe it was a vitamin measurement product) was still 1.5+ years away from release.
That's true LL if: a) there aren't any dropouts, b) there aren't any patient delays (i.e., the patient needs to stop treatment due to medical concerns - unrelated to ava6k), c) they aren't looking to add patients beyond 4.
There has been a lot of discussion recently as to why Avacta chose to present the P1a results so far, instead of waiting until the end of the 3-weekly dosing (i.e., the end of C7). Some ideas include: external influence by a potential partnering company (i.e., they wanted the data out), timing to hit a major conference, etc.
However, in light of what we learned yesterday, that the patient selection criteria for the bi-weekly *and* C7 has been changed to focus on patients with little or no previous cytotoxic treatment, there may be a more straightforward reason.
By changing the selection criteria they expect to maximise the chance that a patient responds to ava6k. But in so doing, they are limiting their potential patient pool massively. There are only a handful of patients that would be expected to be available for a P1a trial (i.e., terminal) with little or no previous treatment. If you think back to Science Day, Prof. Twelves even said the fact that the trial had not included many patients which might be expected to show a response was his fault, and that the reason was that if they would have made that restriction, only a few patients would have been dosed up to that point, instead of the ~20 that they had.
So Avacta knew that with the new selection criteria, they would have a more restricted patient population, so C7 would likely take longer than the other cohorts. Hence, C7 may not end until mid to late Q1 (or perhaps even Q2), which is not something that they wanted to wait for. In this case, it makes perfect sense to present the C1-C6 results when ready and "as much of C7 as possible up to the cutoff date."
While C7 will likely take much longer than C5 or C6, the focus on (near) first line patients could lead to some spectacular results for the patients.
@gmcc - thanks for this, and all your other, posts. Can you give us a bit more detail on your email exchange with AS? i.e., in what context exactly his comments were made? Thanks!
With little or no previous cytotoxic exposure, and the very high dose of ava6k given, we may hear some pretty remarkable stories from C7. Similar to, or better than, the 65% tumour volume reduction that we've already heard about.
We may get some great media coverage before the end of the 2nd arm of Phase 1a yet.
Exciting indeed!
Ok great, thanks! I had missed that...
Hey @icecool and @PL, why do you think that C7 has a change of protocol? I may have missed something. C7 might have a patient with no prior treatment (as the range goes from 0-7), but equally likely the '0' patient may have been in C5 or C6.