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Major media attention will not come until a clear benefit in humans can be shown. This is likely to happen at the end of P1b (unless we get an unexpected surprise in the final cohorts of P1a).

Hahah...nice one R-R! spot on.

Hi GMCC, what email address did you use (i.e., the standard contact of Avacta or the CEO directly)? Thanks. I may fire off a few questions myself.

Also, given that the median number of cycles was just two, there aren't going to be many that continued past the end of each cohort.

I, for one, hope that patients can continue getting dosed if benefits are seen. But I doubt that any info beyond the pre-defined cohort duration would be included in the trial, so it would just be for the patient benefit, not for trial benefit.

Great find MrR. Read this next to Myles' note (pg. 25 - 27).

Comms are dire yes, and some details need to be kept close to their chest. But there are some basics that can easily be discussed. For example:

-ava3996 results, these were shown, great. Now discuss them and what they mean.

-ava6k: they gave the level of dox in the tumor after 24 hours. Oncologists and chemists at major pharma companies will know exactly how to interpret this. PIs (including me, after hours of searching) do not. How does this compare to standard dox at this time? What is the implication for the previous 24 hours where the dox level is likely to be much higher? Again, how does this compare to standard dox?

-ava6k: they gave us the plasma/tumor dox ratio. Again, big pharma will know exactly what this means. PIs don't. How does this compare to standard dox? Or how does this compare to the mouse models?

-i agree that things like FAPa level vs. dox concentration is something they want to keep hidden. As well as linking dox levels to tumor types, or previous treatments, etc. But they gave us the numbers that are basic to big pharma (so they aren't being hidden)...but they mean precious little to us PIs. A little context would go a long way. For example, the poster last april. Without any comment, the info in the poster would have meant very little to us PIs. But Alan's 10 minute summary took us from 50p to 150p in just a few weeks.

@RAH, I completely agree. Why the results aren't being packaged for PIs is a mystery for me. Science day could have easily had 5 or 6 RNSs spread out over the proceeding/following few weeks. Why say 'nothing materially new' and put everything together without any translation for the non-expert? Simple comms would have made a big difference. Maybe there is a reason they aren't doing it?

I, for one, am convinced of the medium/long term here and have gone in heavily. But the broader market definitely hasn't. Why? I still think AIM is one major limiting factor. Loads of day traders and rainbow chasers. During the covid times, all of the traders became focussed on just a handful of covid stocks, driving up their price. But as that drew down, they dispersed back into the full AIM market. And the broader UK investment community, doesn't seem to hold AIM in a particularly high regard, so most investors seem to steer clear of AIM listed companies (and probably with good reason in general).

Which brings us to AS's FT opinion piece. I don't understand the details (not my field), but from the article, it was clear that he thought regulations and changes were making it difficult for large funds to invest in 'risky/small' biotechs. As I know little to nothing about this, I'll take his word for it.

My take is that better comms and a more proactive approach to investors could easily take this share above £2. But that's probably about it. To go higher, we need larger funds getting involved and/or a much larger market (i.e., NASDAQ). To get the attention of AIM investors, you need to promise large and very near term revenue. Extremely short sighted. Based on the examples of similar companies on NASDAQ that i've cited before (CRISPR, Intellia, etc), it seems there the timeframes are longer and potential is valued heavily. Sadly, that's just not the case on AIM.

So yes, 'thick as mince' is about right, because they aren't interested or even looking. Just mostly traders hoping for a quick jump and sell.

I think it's because dox will kill any cell (by mucking up DNA synthesis) that is dividing when dox is present. A general trait of all tumors is that they reproduce more rapidly than standard cells. So simply by multiplying in the presence of dox, can cells will die.

This would be in contrast to other treatment types that focus on a specific pathway, that may or may not be present in a given tumor type.

Good question RAH. I didn't ask that explicitly, but she did say that if you put dox in any (rapidly reproducing) solid tumor, it was going to 'work', i.e., it will do what dox does. This jives very nicely with the article you posted on CRC over the weekend. Dox works well on CRC, it's just that in order to have an effect on the tumor, they need to use high doses which ends up killing the rest of the body. Up the dose in the tumor while reducing the amount in the system, and you have a game changer on your hands.

On a related point, I shared a train journey last week with a friend who is a research oncologist (an academic, i.e., not in the clinic). Of course i used the opportunity to pick her brain on ava6k and precision more broadly (she was not familiar with Avacta). I learned a bunch about cancer development and treatment, most of which is not directly related to avacta.

However, she confirmed what many of us had previously assumed, that dox is effective on a much wider range of tumor types than it is typically used for. The reason why it isn't used more broadly is solely due to the side effects. Basically, dox kills any rapidly reproducing cells, of which cancer is a typical example. Not all cancers, of course, but she pointed out that cancers that aren't rapidly reproducing are generally not the ones you need to worry about. Hence, she expected (assuming the mechanism of action worked, i.e., concentrating dox in the tumor at the expense of the system) that ava6k would be very effective against a wide range of tumors. Interestingly, the two examples that she gave were pancreatic and colorectal cancer (CRC).

This goes some way in defending my view that the potential market for ava6k dwarfs that of standard dox.

Hey RAH, great points. FWIW, my view is that they had already decided to apply for ODD before C3. ODD would have been applied for near the beginning of July, and C3 only started in June, so that's not enough to to see a strong result and write up an application. The fact that STS is treated with first line dox, which has only limited success, and it is FAPa rich means that STS was a primary target. The fact that they get ODD on top of that is just the icing on the cake. Before the trial began, pancreatic cancer (FAPa rich, terrible prognosis) was discussed by AS a few times. I wonder what happened to that.

On the other point, I agree with you fully. They would not change the trial structure nor have a comparison arm if the data so far didn't show a massive benefit over existing therapies. This is extremely bullish and in my view, clearly points to rapid (although likely limited) approval after P1b (with of course ongoing P2 trials).

They did RNS the ava6k poster presentation last March (late March). Was the abstract available before then? But yeah, it definitely seems that avacta have an rns aversion these days when it comes to results.

Great minds think alike....

In the hopes of avoiding another day filled with name calling and discussions over valuations, as Myles just noted on twatter, ava3996 has an MTD in rats that was 6x higher than straight Bortezomib. The pre-clinical studies showed 6x higher MTD for ava6k than for straight dox. Hence, the data are "very consistent" (TM).

This is exceptional news. This is yet another, although important, indication that avacta have really cracked the problem with precision. It does what it says on the box. They can simply add on nearly any warhead and have it delivered to the tumor microenvironment, drastically reducing systemic exposure. It works for ava6k, it works for ava3996. It will work for the others.

Very nice RAH. And that is being extremely conservative. The bull case is that dox is extremely effective on a wide range of (FAPa rich) tumors, which it is not currently the standard of care for, simply due to the cardiotoxicity amongst other terrible side effects. So once AVA6k is available, it will not only replace standard dox, it will see its use skyrocket.

For example, colorectal cancer. The mice models were effectively cured with ava6k, and the tumor type of colorectal. Breast cancer is often treated with dox, as well as keytruda ($18B per year) and others. If ava6k does what it says on the box (TM), then ava6k takes the current dox market, multiplies it by 3x (number of courses), multiplies it by 2x (patients over 60 than can't tolerate dox) and then multiplies it by 10x as it can now be used on a wide range of tumor types (remember that STS is suitable for orphan drug designation because so few people are affected by it...and yet it is still a $300-600m market...think what the breast cancer market it).

So whether the multiplier is 8.9x or 4x or 20x doesn't really matter. If ava6k does what it says, the total accessible market is mindblowing and multiples of the conservative estimates of RAH above.

How's that for a ramp? Rampy yes. Based in reality? Definitely conceivable.

In all the excitement of science day and the subsequent study of the presentations, somethings got overlooked. Correct me if I'm wrong, but last summer, I believe we were told that there would be an update on TMAC and that it was implied (or maybe said directly) that this would happen during science day. In the slide deck, there is just 1 slide on TMAC (slide 25) and it is more of an intro to the concept rather than an update on this platform. Hence the update is still pending. Add this to the list of potential RNSs to drop anytime.

Going back to the good old LFT days of Autumn 2021, AS stated that they were massively upgrading their affimer production capabilities onsite, and that they would be able to produce enough affimers for all the LFTs. I believe that this was supposed to be ready by Dec. 2020. So I don't think production is going to be the problem. Of course with any inserted drugs (rather than ex-vivo LFT types) there are much more stringent controls on who/where these can be made. So that's anyone's guess really. But there are companies (not necessarily large pharma) that specialise in exactly this, making high quality, low quantity drugs for human in-vivo tests.

Great point VS. While I have been wrong every time that I have commented on where Avacta are in terms of the cohorts (I thought that when they finished the first cohort they were actually on 2 or 3...and just hadn't announced it...and I thought the same a few months later), I find it hard to believe that the study would be paused for 2+ months. It's easier to believe that they have continued onto C5 and just haven't told us the dosing levels. But of course it's just guess work.

I would even go a step further. In their Dec. 19th RNS they stated "The Company will update the Market on progress in this study in early January 2023, in advance of the Science Day." To me, this signalled that C4 had already finished by this date (they wouldn't commit to releasing the update if it was possible that they would have to bring in more patients if something went wrong). So it is conceivable that C5 had actually started sometime after Dec. 19th and before Jan 17th. Maybe just me being hopeful though...

Good morning RAH. How do you take away that Avacta are trying to "retain everything in Tx" based on these appointments? Part of her description is: "...with the sole focus of creating maximum value for the organisation’s stakeholders." To me, that implies the difficult task of resource allocation (more money/teams to work on say Precision rather than Affimers or vice versa, and TMAC, etc), which in turn will be linked to license deals (i.e., which to keep in house and which to let out).

I tend to agree with you RAH. Just wanted to point out that it was possible. One note though, is that starting to dose patients where dox is expected to work (i.e., STS), even if it is "only" 200 mg/m2 (which we know is significantly safer and we can infer that it is likely more efficacious) may be helpful in brining the timeframe forward with the FDA for accelerated approval. i.e., showing that "it works" with arm 1 while arm 2 is running with the optimum dose.