Member Info for jive_turkey

Thanks a lot. I just tried to buy some with my US account (Schwab) and it doesn't look to be possible. It finds it and quotes a price (with a 17% fee on top) but says that such transactions with international companies are not possible. So while some might be able to buy/trade Avacta from over the pond, it is a significant hurdle to most.

@RAH, thanks, somebody had mentioned this before, can you explain what this is exactly? I've had family and friends in the US try to buy Avacta shares (through major investing centres like Schwab) and no one has ever been able to.

@York, that's not really a concern nor a mystery. Americans can't buy stocks listed on foreign markets, at least PIs can't. Presumably large funds have some restrictions on this as well. This is the whole idea behind either a move to nasdaq or a joint listing.

@PL, it's true that it was at 6x the dosage, but the ratio of dox in the tumor to the heart is independent of the dose level. The dosage only comes in if you ask the question of how much dox is in the tumor relative to the standard dox dose. So the comparison of dox in the tumor/blood or tumor/heart is a set ratio, hence 18x is the standard to compare against.

@honoihank, that's a good point and needs to be taken into account for a lot of comparisons, but I don't think that it does in this case. Check out slide 13 in this presentations (right panel):
https://avacta.com/wp-content/uploads/2022/04/Avacta-Group-plc-Prelim-Results-2021-FINAL.pdf

This is doxorubicin exposure, so the molecular weight doesn't factor in (i.e., this is the dox present after cleavage).

It would seem prudent to cover more bases by selecting at least 2 (if not 3) tumor types for P1b. Especially as the TAM for STS is relatively small. It will make more of a splash if breast cancer is selected, although there the competition is tougher.

What data could we reasonably assume will be released/discussed on Science Day? Some of the rainbow chasers have suggested tumor size shrinkage and/or other measures of efficacy. This is extremely unlikely in my view, as these are measurements that must be made on a patient population, i.e., not one patient at a time. The patient pool at this stage isn't large enough to have these kinds of numbers (19 patients spread out over multiple cancer types).

If we go back to the poster presentation from last April (in the summary/presentation by Alan), much of the data presented (based largely on rats) can't be presented on humans (yet), i.e., total survival rates, tumor sizes vs. time, etc. However, much of the pharmacokinetic data is accessible. This is a key focus on P1a and useful information to give out (to investors and the industry). So I believe that we will see (at least) 1) C_max (the maximum concentration of ava6k, the leaving group and dox in the blood) and 2) AUC (the area under the curve of the concentration vs. time, again for ava6k, the leaving group and dox in the blood).

This will show that ava6k isn't cleaving much (but there will be some) in the body, which will prove that ava6k is safe. In rats, C_max was ~48 times higher for ava6k than dox, while AUC was ~8.7 times higher for ava6k than dox. So these are the numbers that we can compare directly to. If these ratios are higher in humans, then the drug is even safer for people (less systemic FAPa) than for rats, and will imply an even higher ratio of dox in the tumor to the blood for humans.

But the big number that we all want to see is the ratio of the concentration of dox in the tumor to the concentration in the blood. In mice, there was 18x more dox in the tumor than in the blood (by concentration). Again, given the lower levels of systemic FAPa in humans than in rodents, there is good reason that this ratio will be >18 in humans. For the 6 patients where they have biopsies, they have measured this ratio. In the interview, Alan stated that there was significantly more dox in the tumors than in the blood....but how much more?

I believe that it is this ratio which is the key to the results. A factor of 2 is great. A factor of 10 is amazing. A factor of 18 reproduces the mice models which were world changing. A factor of >18....well, that's just off the charts.

So the big question is, will they present this magic number? Or will they hold it close to their chests until a big oncology conference this spring, or even hold it until the end of P1a? For my money, it is this ratio that will seal any deals, and will generate massive interest from the industry, assuming that it is positive of course.

Thanks BV, DTW and WAG for the responses, very helpful!

Here's a question for the experts (or perhaps those better with google than I). There are a (large) number of different chemotherapies out there, and each one has their own specific mechanism of action. This results in different, or at least to different levels of, side effects. My understanding is that different chemotherapies are used for different cancers and in different combinations because 1) different cancers respond differently to comparative chemotherapies and 2) because they have different side effects, so clinicians can mix and match chemos to 'spread out' the side effects, especially the serious ones like cardiotoxicity and neuropathy, to extend life while hitting the cancer multiple ways.

Ok great. But let's say that a company was able to develop a 'side effect free' (or at least greatly reduced) chemotherapy. Just hypothetically, of course. Let's also assume for this example, that the chemo that this new technology was applied to was doxorubicin. Doxorubicin is typically used for breast cancer, ovarian, leukemia and a few others. But I assume that this is limited by the side effects. Could this magical new form of dox be used for a wide range of other (FAPa rich) cancers?

So the question is, how many other chemos can precision be applied to, in practice? Yes, Avacta have 12+ lined up where they can apply the technology, but will this be needed? For example, Velcade appears to have a very different mechanism of action than dox, and it isn't used for solid tumors because the side effects are too great. So there seems to be a clear commercial to develop this after dox (hence ava3996 entering pre-clinical trials after ava6000 mechanism of action was confirmed). But what about other anthracyclines, will they be needed (if ava6k works as we expect)?

So the question can be cut two ways. First, practically, how many chemo drugs (or how many different mechanism of cancer destruction) would be commercially viable for precision to be applied for?

Or to turn the question around, what is a reasonable total addressable market for ava6k (or ava6k + ava3996)? The numbers that have been thrown around are typically for just three cancer types. And, as we know, if you increase the dosage allowed per patient, you can double or triple that market. Plus then you can also target older people or people with underlying health conditions, so that is an additional factor of two or three. But what about applying this 'new dox' to a wider range of other cancers than dox is typically applied to? This could dwarf all the previous multiples.

Next summer, as in 4 months from now.

Oh dear, hurstbot appears to be malfunctioning....spouting random numbers.

It would never make national news if the company refused to do interviews supporting the story. The question is when will they start to shout about the P1a results. The three possibilities are: 1) science day. 2) at one of the major international oncology conferences in the Spring (AACR or ASCO) or 3) when P1a finishing sometime next summer.

FWIW, I was leaning toward 3 originally, but now think 2 is most likely. I think we'll get some great bits from 1, but it won't be the full media splash...which will come later.

Maybe a US trial site coming online - if the William Tap tipoff is correct....

binned

@swarof, just to put your note into context, in fact the LFT was approved (for professional use) around that time and a few months later it was approved for home use. Based on the published S&S results, Avacta's lft was in fact the most sensitive in the world/on the market. Hence, that statement was true and it was also true that Avacta were able to develop an extremely sensitive test that was world leading.

It was then later pulled due to the excessive changes in the omicron variant and also due to the fact that the market for covid lfts shrunk massively, as the omicron was much more mild that previous variants. Those events came well after the fact.

Eggy, it's great that you have thoughts to share (well done you!), but before you do, you might want to revisit the results for the mouse models (which went four times higher than standard dox), or if you don't want to actually look up the results, please see the dozens of times this topic has already been discussed.

BV, I had never seen the graph of the number of buys/sell during the day, but it is interesting that it drops around 2 or 2:30 UK time. Is this common throughout AIM or Avacta specific?

I had noticed, however, that the SP very rarely significantly changes around 14:30, implying that the presence or absence of US traders has little impact on Avacta. And the number of times we were told about 'Bego on the bid' (still not sure why the bot thinks that is relevant) and that the SP was about to jump, whereas nothing of note happened, is high. Personally, I like Timster's theory, that Hurst is a bot that posts random, although optimistic, things...an AI bot trained on a wikipedia investment page.

And as we all know, companies in a death spiral tend to go on large hiring sprees to hire large numbers of the best and brightest, just for the satisfaction of sacking them in a few months time.

Personally, I don't think that lack of trust in Alan is a significant issue for the SP. Yes, some of the FUDers will bring this up and quote the LFT situation without context, but that's not a major hangup, in my opinion. Nor is there a significant pool of investors 'waiting to see the data'. As you say RAH, they wouldn't understand the data if given to them.

The main issue, also brought up by the CEO in his opinion piece today, is simply AIM. There are a finite and relatively small pool of investors (private and funds) that bounce around AIM. The covid days were unique, in that a large fraction of these AIM private investors were all thinking about how to get rich quick off covid, so they all rushed in to 5 or 6 companies that had various covid related programmes. All of these companies had a spike in the SP during covid, and all but Avacta have fallen down >90% since their highs since the investors then fled once the 'get rich quick' period ended (i'm thinking ODX, ABDX, GDR, NCYT). These are typically not long term investors, who jump from share to share, chasing the newest thing. It's all about high risk, short term investments that have a chance to have a massive spike overnight. Hence, the fascination with small cap oil and mining companies.

Hence, the only way to get attention on AIM, in order to have a proper valuation of precision and the rest of the company, will be to bring in a large new pool of investors. For me, this will happen once Avacta hit the main stream media. Most of the people I know in the UK who invest (long term holders, typically largely mutual funds, with a few individual companies) have never heard of AIM nor of Avacta.

So there just isn't strong, stable and long sighted investor base on AIM. This is what is provided by going to NASDAQ, as well as access to larger funds that specialise in biotech.

As I wrote back in December, a good comparison can be made between CRISPR Therapeutics and Intellia Therapeutics. These are both pre-revenue companies (in this case, both in gene editing) that aren't expecting to have a 'blockbuster' drug for at least another 6 or 7 years (their first generation of drugs go after small 'niche' diseases to prove the technology and get over regulatory hurdles regarding gene editing). Both are 'unicorns' being valued at $3.5-4 billion. If these companies would have announced "chemo without side effects" they would have double or tripled on the announcement. Such is the investor base that they have access to.

IMO, a NASDAQ listing and/or a front page BBC article with an example or two of a terminal patient that had a miraculous recovery due to ava6k, would both result in a massive re-rate.

For what it is worth, I think that it is pretty clear that we are no where near the MTD. As stated by Alan in the interview, even cohort 4 did not display any serious side effects or toxicities. Toxicities tend not to be binary, i.e., it's not 'everything is ok' vs. 'severe toxicity', rather the degree and occurrence increase as the dose amount grows.

Great point Energy. It would be interesting to know where Point Bio is in the development process. Early days, of course, but could they announce preclinical IND enabling studies, or is that still a ways off. I was even considering buying some Point Bio shares...but would need to do a lot of reading as I'm not overly familiar with their non Can-seek stuff.