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@MS- My understanding is that they don’t have a core holding of 40m. Each quarter Avacta issue new shares (about 3m or so), in order to repay part of the debt and interest. So each quarter they only have 3m shares to sell. This is only a very small fraction of the total trades (even over a week), so they cannot be the cause of the volume.
I agree with Starbright’s take. All this talk of Heights is just a red herring.
Because a competing drug developed by Bluebird Bio for Sickle Cell Disease was approved on the same day. This other drug was expected to be approved in late December, so I think it stole the thunder from Crisper's announcement.
@Starbright - yep, 3m per quarter. But the important point here is that there are 1-2+ million of shares traded every day, so the conclusion is that Heights are not selling the 'big blocks' that we've been seeing (unless if they have been saving their previous quarters' 3m shares, but the excuse that Heights selling has been used every time they get allocated shares). The volume that we are seeing is much too high for Heights to be making up a significant fraction.
@York - Unfortunately, i don't see how they can give us much more information about partnering. Until a deal is made they wouldn't want to show their hand which could potentially hurt the negotiations (i.e., if they let it be known that they needed a partner for P2, that weakens their position if the other company knows that it is needed, not just preferred). So I expect more very broad brush statements.
@B2HS2L - Yes, this is an excellent point. This won't be commenting on PFS directly, but they will have loads of data on tumour size through CT scans. This was pointed out to me yesterday by Marty McFly on X/Twitter (and I believe he will post some great insight on this early next week, i.e., what we can expect). But basically, it seems reasonable to expect that we will see how many patients (probably broken down by Cohort) match each of the RECIST criteria, i.e., partial response (PR), no response (NR), and progressive disease (PD). This will allow us a direct comparison to straight dox and other chemos. Unfortunately, it suffers from the same problem of mixing tumour types, but Avacta are clearly taking this data.
@BITL 8.9 months - https://clinicalsarcomaresearch.biomedcentral.com/articles/10.1186/s13569-020-00137-5
But you are right, I think that this is a biased cohort, because it is patients that were able to tolerate 6 doses of dox. Indeed, it is often quoted as 4-6 months.
@icecool - yes, PFS is a very common surrogate end point. However, the PFS time varies a lot between different cancer types. So you can't estimate PFS for a combination of say STS, colorectal and ovarian patients. They all have to be the same type.
And for C6, indeed they are coming up on 6 months (and my belief is that many/most of that cohort will still be on ava6k and will have still not seen any progression. So right now, their PFS (assuming that they are all STS patients) is 6 months, which is below the standard for straight dox. So this isn't impressive at the moment.
I fully agree with accelerated approval, but I think that will come at the end of the bi-weekly dosing. The FDA wouldn't approve a drug before the dosing and schedule are worked out.
@icecool - Indeed, if Avacta can release some figures for Progression Free Survival (PFS) that would well and truly blow the bloody doors off. Unfortunately, I think this is unlikely at this time though. The PFS time is ~8 or 9 months for STS patients when beginning on straight dox. This means that only Cohorts 1-4 would have had enough time to go beyond this. But in C1-C4 there was only one STS patient (C3). And one would not be enough to estimate PFS from (as there are a wide variety of responses to dox).
From the clear response that we've heard about for ava6k in C5 and C6, I would expect PFS to *at least* double for ava6k relative to straight dox for STS patients, and the Overall Survival Time to possibly be much longer. However, that is at least 1-2 years away for PFS (longer for OST) and that is assuming that C5 and C6 have enough STS patients to estimate this.
Nope, just online.
"I believe that we are on the verge of a paradigm shift in how chemotherapy is delivered to cancer patients." - AS, Sept 19th RNS
Hmmmm...I wonder....
@CJ - are you advocating selling the therapeutics division (Tx) and just keeping diagnostics (Dx)? That seems controversial.
I don't think a sale of the Dx division is likely, AS mentioned possibly spinning it off as a possibility.
Also, I don't think Takeda is more/less likely to partner on ava3996 than other BP. Remember, ava3996 is not a pro-drug form of Velcade. It is a pro-drug form of an analogue of Velcade. So it has nothing to do with Velcade or Takeda. As BV has pointed out, Velcade lacks to the key chemistry to be directly used with Precision, which is a shame as if it did, then a lot of the pre-clinical work (i.e., showing that the warhead, ava2727d, is effective) nor Phase 3 would be necessary.
Update:
Almost certainly we will hear about:
-An introduction to Precision and ava6k
-Patient demographics and cancer types (effectively an update of slide 81 from the science day presentation), total number of patients in each cohort.
-Detailed PK results, along with interpretation and comparison with dox.
-Side effects profile (update of slides 82 and 83).
-Biopsies update (update of slide 84), hopefully a nice plot showing concentration of dox in tumours vs. dose level (i.e., demonstrating dose dependent results).
-Individual case studies (the patient with STS with large tumour reduction along with others, hopefully also saying which other tumour types have responded).
-Perhaps more detail on whether/how many patients are still receiving ava6k and from which cohorts and cancer types.
***-A discussion of the (complete?) lack of cardiotoxicity, how this is measured, and what this could mean for the number of cycles (lifetime limit) of ava6k given. This should be directly related to the Progression Free Survival (PFS) timescale, although I doubt that they will estimate this from the data in hand.
-An update on the bi-weekly trial (has it begun, if not, when, what is the initial dose level?).
-Perhaps a slide on the planned Phase 2 study structure.
-Likely a general comment about an uptick in commercial interest with no details.
What we are unlikely to hear about:
-Potential commercialisation and license deals as these will not be commented on until they are made (you don't discuss them until they are finalised), which may only be days/weeks away after the P1a data are released.
-Partnerships for P2 for STS or other indications (same as the above, no discussion until deals are final).
-Plans for media coverage, other than 'strategy is in place' (again, you don't comment on something that you have no control over, otherwise it could look like a failure).
It is unlikely, but possible (if the data are good enough) that they could give us a response rate (ORR) for Cohorts 5 - 7 (assuming the majority of the patients are STS). But this is likely wishful thinking.
@RD - Yes, median number of cycles would be good to know...I guess this is tied in to if an how many patients remain on ava6k.
I'm sure that they are measuring the percentage of ava6k cleaved into dox based on urine samples, but I don't think that this tells us much about dox concentrations in the tumour. E.g., let's say they find that it is 100%. Ok great, but how much of that was cleaved systemically (i.e., in the blood/normal tissue) and how much in the tumour? If ava6k is cleaved systemically, over multiple days (instead of just getting a shock of dox in the system like when naked dox is given) the concentrations in the body might remain quite low (tolerable) even if the total amount of dox over time is relatively high.
Also, I'm not sure if they can reliably estimate how much total exposure of dox in the tumour, given that they will only have 1 (or 2) time points per patient (i.e., 1 biopsy). For animals these can be taken at regular intervals to see how much dox as a function of time is there, and integrate.
However, you're spot on with the estimate of how much systemic exposure there is (through blood samples and modelling). From this they will be able to estimate how many cycles are possible. Especially when combined with independent estimates of cardiotox.
Almost certainly we will hear about:
-An introduction to Precision and ava6k
-Patient demographics and cancer types (effectively an update of slide 81 from the science day presentation), total number of patients in each cohort.
-Detailed PK results, along with interpretation and comparison with dox.
-Side effects profile (update of slides 82 and 83).
-Biopsies update (update of slide 84), hopefully a nice plot showing concentration of dox in tumours vs. dose level (i.e., demonstrating dose dependent results).
-Individual case studies (the patient with STS with large tumour reduction along with others, hopefully also saying which other tumour types have responded).
-Perhaps more detail on whether/how many patients are still receiving ava6k and from which cohorts and cancer types.
-An update on the bi-weekly trial (has it begun, if not, when, what is the initial dose level?).
-Perhaps a slide on the planned Phase 2 study structure.
-Likely a general comment about an uptick in commercial interest with no details.
What we are unlikely to hear about:
-Potential commercialisation and license deals as these will not be commented on until they are made (you don't discuss them until they are finalised), which may only be days/weeks away after the P1a data are released.
-Partnerships for P2 for STS or other indications (same as the above, no discussion until deals are final).
-Plans for media coverage, other than 'strategy is in place' (again, you don't comment on something that you have no control over, otherwise it could look like a failure).
It is unlikely, but possible (if the data are good enough) that they could give us a response rate (ORR) for Cohorts 5 - 7 (assuming the majority of the patients are STS). But this is likely wishful thinking.
Yes, the "chemotherapy without awful side effects" would definitely gather some interest in the MSM, but I think a relatively small amount compared to "Miracle breakthrough in cancer treatment, patient given months to live now home, cancer free, in time for xmas".
However, for the MSM, "miracle breakthrough" is actually a relatively low bar to clear, amusingly. Look through articles "cancer breakthrough" is UK media, and you'll find that increasing the ORR from 20% to 40% would fall under this category, ***as long as one or a few patients have seen the tumours obliterated***. That last bit appears to be key.
Good question Timster. I don't know the answer in general (perhaps it goes both ways?), but in one example from "For Blood and Money", it was the big pharma company (Johnson & Johnson) who contacted the small biotech (Pharmacyclics) after they had seen some of the results. Interestingly, after initial discussions to gauge interest, Pharmacyclics allowed the higher ups of J&J into a secure room with a computer to look over all of the trial and pre-clinical data in detail. Presumably some NDAs were involved. It was implied that other big pharma companies also had such access and that J&J simply made the best offer.
@DTW - as has been lamented by AS and other AIM/LSE CEOs, there just aren't the large funds and investors in the UK to properly support early stage UK biotechs. This includes rules about risk (and market cap) for pensions and other large funds. Additionally, the pool of PIs willing to swim through the cesspit that is AIM is relatively small. You could grow this by a factor of a few if Avacta's same was front page BBC/Sky news, which is likely to happen if some good 'feel good' stories can be brought to the main stream media.
Beyond that, we need large backers, either a large pharma taking a significant stake, or large international investors (likely coming from the US). This is where the real value lies, and I'm confident that this will begin once the P1a data are made public and deals begin to be made/made public.
All assuming that the P1a data are as good as we all expect.
On May 25th, 2023, Verastem Oncology (Nasdaq listed) announced the results of a Phase II trial, where their drug (avutometinib) was paired with an existing drug (defactinib) to treat "recurrent low-grade serous ovarian cancer". The overall response rate of the study (29 patients) was 45%. On that day, the share price just 120%, and the data were presented in a poster at the 2023 ASCO (June 2nd). https://investor.verastem.com/news-releases/news-release-details/updated-data-part-verastem-oncologys-ramp-201-trial-show
Once the data were presented at ASCO (June 3rd), the story was picked up by the media that day and generated some impressive headlines (e.g., https://www.theguardian.com/science/2023/jun/03/new-drug-combination-offers-ovarian-cancer-breakthrough).
I mean to give this only as an example of how things could play out over the next few weeks. i.e., data release with top line results in an RNS, followed by data presentation at a conference, which then leads to significant media coverage.
Beyond that, there is little to compare between Avacta and Verastem Oncology. Verastem effectively have a single drug (avutometinib) and are running multiple trials of that drug in combination with other drugs to treat various cancer types. There is no pipeline, and definitely no broader platform. After announcing the results, the stock price has dropped back to near previous levels, I guess as it became clear that the results are good, but are definitely not providing a paradigm shift in cancer treatment.
This is the abstract of the poster presented in Boston in Oct. 2023, all of the abstracts have just been published. So no lighting of the blue touch paper yet. But soon.