Member Info for jive_turkey

@RD, we (or at least I) keep coming back to the 3x more dox in the tumor with ava6k than standard dox, simply because this is the baseline from the pre-clinical studies, so it's our best guess at the moment. This is the question that I wrote to AS with, how much dox is typically in the tumor at 24 hours and his response was "it's not in the literature, so we don't know." But he did stress (based on the data presented in the table in the SD presentation) that there should be more than enough dox in the tumour for a therapeutic effect. There are reasons to think that it could be better in humans (less free circulating FAP) than in mice, but there could be confounding processes.

As has been noted on the board previously, if there is as much dox in the tumour with ava6k than with straight dox (for comparable doses) Avacta are sitting on a blockbuster. If there is 3x more than Avacta are sitting on a revolution.

And from the mouse PK data for ava3996, the results appear to be even more targeted than ava6k.

@Neutronic, yes that is the conclusion I've come to as well. Normally, the SP should be rising every time the pipeline is de-risked. It's just not happening here. So it's not so much that the market is thick, it's that the market just isn't paying attention.

@MrR, note that in C1-C4, the medium number of doses was just 2. So the patients (in the majority of cases) did not proceed to anywhere close to the maximum allowed cumulative dose. So in principle, it seems that 6 weeks would be enough per cohort.

We know that a patient in C5 just received their first dose (RNS yesterday), so we'll see how long before this cohort completes and C6 begins (which I have little doubt will happen, i.e., MTD will not be found in C5).

As always, note that what is meant by precision in this context, is *not* the precision used by Avacta. This is referring to gene/patient specific targeted therapy, while Avacta's precision is a general chemotherapy.

However, this does raise a good point. If ava6k and ava3996 work as well as we think (that we have indications and early results from) this is going to have a massive impact on the development and money making of other therapies. As AS has said, ava3996 looks to be a 'tumor agnostic therapy'. If this is successful, this is going to cut out a large number of alternative therapies, dramatically lowering their revenue stream.

While I doubt that big pharma are currently cutting back on their estimates of revenues from the current and future drugs based on Avacta's precision (it's still early days) they will over the next year or two as the efficacy studies enter the public domain.

Thanks MrR, spot on. It also happens to ignore what happens in other markets (i.e., Nasdaq) for young biotechs. There, investors know that future raises are possible, but the SP grows as the products are de-risked. If his theory was correct, then we should see more investment after a raise on AIM, because the time till the next rise is the longest.

250mg/m2...the same across the entire C5 cohort.

@RD, you wrote "SP will rise on facts rather than inference." While this should be the case, unfortunately it is demonstrably untrue for Avacta. They have released a lot of facts recently, i.e., ava6k works as designed (dox deposited in the tumor at therapeutically relevant levels), drastically reduced side effects, no MTD found to date, US hospitals coming online, ava3996 first results are extremely positive, etc etc etc. And yet, the market is not reacting. It is clear that facts will not help, as there is simply not enough liquidity nor large investors on AIM. Even if a license deal is announced, the bounce will be subdued. From what I've seen on AIM, the only chance of a realistic valuation will be a take over offer, a US listing, or a miracle of a few large UK funds taking a stake (which from what I can gather from AS's FT article, is restricted due to regulations and generally being risk averse).

2727 is just the warhead. It is toxic, very toxic, just like velcade. But it is a 'new' warhead, hence they also had to demonstrate its effectiveness.

I agree gmcc, at the science day he seemed to be the most enthusiastic, really pushing how great ava6k was. Great to have him on our side.

Actually, there is FAPa expression in the bone marrow, which is the origin of blood cancers. So ava3996 could be used for this to some degree. However, I believe that the point that AS was making was that the market for velcade is quite limited, effectively only to multiple myeloma, as it is too potent to use for solid tumors (due to the high levels required to get into the solid tumor). However, ava3996 solves this issue, so the market that ava3996 can target is orders of magnitude higher than velcade. And velcade is worth ~$2 billion per year. A tumor agnostic chemotherapy with limited side effects is a $20 billion+ per year drug, easily. Keep in mind that keytruda, used almost exclusively for breast cancer brings in $18 billion per year, and the side effects of that are horrendous.

Spot on RAH. There is no doubt that they pick the questions they want, and Fast Track vs. Breakthrough is a good example.

Agreed. The problem seems to be the lack of such investment institutions in the UK who are willing to invest in biotech. See the FT times article by AS as well as the recent article quoting Gabriele Cerrone (CEO of Okyo Pharma). Cerrone said about listing in the UK: "'It has been a complete waste of time and we never raised money from investment banks. There's no biotech culture nor any liquidity in the United Kingdom at all.'"

So i'm not convinced that we will see a substantial re-rate to a reasonable valuation (in my opinion 500p+) until approached by a big pharma.

AS was asked about FDA Fast Track approval for ava6k. His main response was that they are looking at any and all options to get ava6k approval as fast as possible. Great.

But interestingly, he mentioned that Fast Track probably wasn't the best way to get accelerated approval for ava6k. He emphasised this in light that it uses a well known/studied drug, Doxorubicin. So they obviously have given this some thought.

Here are the accelerated FDA approval options:
https://www.fda.gov/patients/learn-about-drug-and-device-approvals/fast-track-breakthrough-therapy-accelerated-approval-priority-review

It seems clear that Breakthrough Therapy is the way that they are going. i.e., demonstrate that ava6k is significantly better than straight dox (both in safety and likely in effectivity) and they'll be golden.

A great little gem from the Q&A.

Agreed. Absolutely excellent in all respects. Kept emphasing that the market for ava3996 will absolutely dwarf that of velcade ($2.3billion per year). As always, I would like to hear about affimer based diagnostic products, but that said, I'm glad they spent the time going through therapeutics and Launch.

In my view, the discussion regarding cash position from the FUDers is just drivel. As OAMOT (and BBN on twitter) points out, the cash position is fine for the near/medium term.

However, this line from the RNS says it all when talking about future funding: "The sources of income could come through the licensing of assets/targets from the proprietary Affimer® and pre|CISION™ platforms or through additional therapeutic collaborations". Remember that the going licensing rate of *pre-clinical* ADC assets is in the hundreds of millions range. One single licensing agreement from precision sorts out funding for the next decade (or course, it wouldn't last that long in practice, as Avacta would use the funds to accelerate multiple candidates, affimer treatments and TMAC into the clinic).

https://www.thisismoney.co.uk/money/markets/article-11987227/London-stock-market-complete-waste-time-says-biotech-tycoon.html

Key quotes:
"...building a biotech company in the UK 'is like trying to grow plants in the desert'. "

"'It has been a complete waste of time and we never raised money from investment banks. There's no biotech culture nor any liquidity in the United Kingdom at all.'"

"in the US 'there are loads of hedge funds, high net worth individuals, analysts and a whole culture of wanting to invest in biotech which doesn't exist here'."

A bit more of a direct way of saying what AS said in his FT opinion article. Seems to be a trend.

SB, yes you're correct, but overlook a key point. The examples given were NASDAQ listed companies. First, as has been pointed out previously, bio companies on NASDAQ that are a similar stage (for example, CRISPR, Intellia, Editas) who are aiming for similar total addressable markets (TAM) as Avacta are often valued 5-10x more than their AIM equivalnent. That that is a big factor up front. Secondly, as can be seen in Prometheus, the stock jumped 170% in December on the publication of positive clinical results. I, among others, argue that this is perfectly reasonable as the treatment was then substantially de-risked. Note that this did not happen when Avacta released the P1a results so far. Hence, little or no de-risking has been priced in. Finally, in the year before the Prometheus results were published, the SP rose 100%, again as the trial continued, investors felt that it had been de-risked to some degree.

None of this has happened for Avacta. We can argue why, but my feeling is that it is AIM, or possible the UK market in general. As has been noted by RAH and others, while the buyout price can be related to the market cap of the company before buyout (as a percentage), that does not mean that the buyer viewed it that way. We argue that the buyer (and seller, as this is a negotiation) valued to company, both current value and potential future value, and put a price on that. In the US, the potential is valued in the SP as the time to market gets closer (i.e., pre-clinical is worth less than Phase 1, 2 or 3 clinical trials), so you get less crazy jumps (market cap vs. valuation by large pharma). In the UK, this doesn't seem to be the case. But if the product is bought based on likely potential, the end result is the same (price paid), hence the jump from the last open market day to the bought price can be significantly larger.

@Livedata, officially you are correct. However, ava6k worked wonders on colorectal cancer (CRC) in the mouse models and the majority of the patients on P1a so far have been CRC patients.

@Bella, remember that the median number of doses per patient has just been 2 so far in P1a. So no, there probably hasn't been a very large shrinkage for most patients. That said, for the clinicians involved, I am sure that they have a very good idea of how it is performing. Not statistically significant, and need a much larger cohort and more doses, but a strong initial insight.

As most science experiments, the people running the experiment generally can see the results (i.e., positive or negative) well before statistical significance. They don't report it at that stage because in order to convince the world you need the statistics, and of course, you know that things can always change. So you need to run it to the end, but you have a good idea way before then. Based on the selection of ava3996, the move to London, the bringing of US sites online, I think it is pretty clear that Avacta know where this is going.

As we wait for news regarding C5 (and potentially C6 and C7) it is interesting to speculate on what the maximum tolerated dose level (MTD) is likely to be in humans. Back at the science day, Prof. Twelves said that he didn't think that we were anywhere near MTD in C4 (200 mg/m2 of ava6k = 135 mg/m2 of naked dox). On the other hand, AS seems to think that they may be zeroing in on an MTD in his recent vox interview (i.e., unlikely to get to C7 - which we now know would be up to 400 mg/m2 of ava6k = 270 mg/m2 of naked dox).

In mice, the MTD was 6 times that of ava6k than straight dox. This is the equivalent of 4 times the amount of straight dox.

If we take a 75 mg/m2 dose of straight dox as the standard, 4x this value would be 300 mg/m2 of straight dox equivalent. This would equate to 444 mg/m2 of ava6k. So very close to the maximum allowed of 400 mg/m2 set by the MRHA application. If you take 60 mg/m2 dose as the naked dox standard, 4x this would be 240 mg/m2 of straight dox, or 355 mg/m2 of ava6k, i.e., within the range of the allowable dosages set by MRHA.

That, of course, assumes that the mice are directly scalable to humans...which may or may not be the case. The lower systemic FAPa levels in humans may push MTD outside the range. Or maybe they won't push as far in humans as they did in mice (for obvious reasons), i.e., DLTs may be easier to see in human than in mice.

The take away is that both AS and Prof. Twelves may be right, and an MTD may be found in C6 or C7. Based on the above, I would be surprised to find it in C5.