Member Info for jive_turkey

@BBB - luckily for you we already have the answers to your questions. 1) No, patients do not change dose levels. If they start on C4 dose levels they remain on C4 dose levels.

2) Avacta are aware of the FDAs special programmes, and AS has stated that Fast Track is not a likely option. Reading through the details of the different programmes, Breakthrough Therapy and/or Accelerated Approval match our situation much better.

3) It has already been proven to be dox in the tumour.

4) No this is not enough. Equivalent or improved efficacy is also required. i.e. say that dox is in the tumour but at not high enough concentration to do any good. Then it won't be approved. But the data so far seem to suggest very good efficacy, so that is another box ticked.

Can you comment on the relative specificity between ava6k/Precision vs. available ADCs?

@AVCT - Thanks, I'm not too familiar with Nuvalent. Reading up quickly, they released their preliminary Phase 1 data on Oct. 28th, 2022. Indeed that day they jumped up 78% and have been steadily rising since.

Note, however, that Avacta presented their preliminary Phase 1 data in Feb. 2022 (science day) and the share price has not significantly reacted. Our Phase 1 data proved safety and tolerability and proved the mechanism of action. Yet no reaction.

Also note that the Nuvalent treatment looks for mutations in specific cancer types, hence their total addressable market (TAM) is a mere fraction of that of ava6k (although their Phase 1 focusses on lung cancer which is a much larger TAM than STS. And even with all that, they were still double the market cap of Avacta when they released their data.

So in fact this appears to be an excellent example of the very large differences of the US and UK markets.

If there is no media coverage (beyond the Yorkshire Post) alongside the results, then 10-20% increase. If there is significant media (BBC, Sky News, etc) coverage 100-200% increase.

Fundamentally, Avacta's Precision platform is a direct competitor of Antibody Drug Conjugates (ADCs). Effectively, they are both mechanisms to bring a targeted warhead into the tumour and spare healthy tissues. ADCs are all the rage at the moment (with $50B+ of deals in the last couple years focussing on ADCs), although they have their drawbacks (as has been discussed previously), which is where Precision will shine.

Just reading up on the ADC market this morning I came across this article: https://www.pharmamanufacturing.com/sector/large-molecule/article/33006389/the-great-reappearing-act-adcs-light-up-the-stage (from June 2023). Interesting read.

Some key points:

-“We’re definitely seeing strategies where drugmakers are getting into difficult indications initially, building up a safety profile and then sort of walking back to broaden the applications,” says McKee.

i.e., get approval for a specific indication first, then use that as a base to expand into more lucrative tumour types. Check.

-"While ADCs are currently the headliners, leaders in the space point out that they are just one modality under the widening umbrella of bioconjugates. "There is much more than the traditional ADCs,” says Lonza’s Bertholjotti. “New types of novel formats will pop up and that’s also how I see the market further evolving." Check.

-"A lot of factors speak to the evolution of the field, but the deciding factor will be the patient benefit." Check.

Just changing the subject at BITLs request. ;)

@BITL - is that true? I thought we were always given 10+ days? For example, for the September investor meet we were given 17 days notice...

@lor - that is where we disagree. I don't see anything nefarious about people being positive about the company. They are excited about the company, its prospects and its technology. And I am too. Their pumping doesn't affect the share price nor does the de-ramping from others. At least not significantly. Just because they are positive doesn't mean they are trying to inflate the SP so that they can sell and make their 10% profit.

Humans have a need to come up with a narrative to explain things out of their control. Hence, all the stories about MMs manipulating the price (apparently every day it goes down, MMs are the cause), or Heights selling, or a new TR1 buying who want to the share price to be low to accumulate. Or mates rates or whatever. Those things might happen on occasion, but on any given day it is driven by buyers and sellers. Some bigger than others.

Why is the SP where it is? If we compare Avacta to they US-listed equivalents, we are drastically under-priced. But among UK-listed (pseudo) equivalents we are about average or even "over-priced" (if you listen to some of the FUD spreaders). There is less money, less large biotech centric funds, less high net-worth individuals, less venture capitalists in the UK than in the US. Hence, without these larger support bases, Avacta will remain severely underpriced relative to their US equivalents.

Getting media coverage will bring in many more UK based investors which will help. But the data will unlock the possibility that a large US based fund or even a big pharma company will come in with a serious investment, which will be where the real re-rate will come from.

What I don't know is what are the rules for US based funds to invest in non-US listed companies. i.e., not legal rules, but rules for their investors.

@54 - AS said in October (and it was implied in September) that he had a pretty good idea of when the date would be for them to announce/release the data. So the date has been known for quite some time (within the company). This would also be why it wasn't clear whether, or how much, of the C7 cohort would be included. It depends how far they are with that cohort. The RNS last week was simply because Investormeet requires a given amount of time (presumably 10 days) to prepare for the online event.

Hopefully this is organised around a media push as well. We'll see.

@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.