While the ~20% rise in the SP is definitely appreciated, it is a joke given the news that we have received today (along with all the news over the past 2 years). Imagine AZ or Novartis issuing a statement that a drug in development is going to essentially skip P1b and move directly into P2 as it has shown significant efficacy and an unbelievable safety profile. Their MCAP would not lift by ~$50M....rather, it would be in the billions.
We all know the limitations of AIM, a large contingent of short-term investors and rainbow chasers. Also, the Financial Times opinion piece by AS strongly suggested a general problem in the UK markets, either not being allowed to invest in early-stage biotechs or being too risk adverse. As AS stated (also see the links by BV), the US doesn't suffer from this problem, it has individuals, funds and companies that look for early stage - high potential - biotechs.
So why aren't they getting into Avacta? I don't know, but I have a pet theory. While Avacta have put out results to the investment community (i.e., science day, the C5 end RNS, today's RNS, etc) none of it has been officially published or presented to the scientific community. I wonder if this could be holding back the big boys. Maybe they require, or strongly prefer, results put out in the scientific literature, where known scientists are putting their reputations behind the results.
With that in mind, I note that their is an AACR meeting in Boston in mid-October. Avacta have 2 abstracts (one for an affimer study and another for ava3996) for posters. However, it is also common for big results to be held back until the week of the conference, i.e., if Avacta have a talk to present the ava6k results it may not be released until the week of the conference.
This may just be optimistic thinking, but this could be an excellent opportunity to present the clinical results of ava6k to the scientific community. We won't know for certain until October. Otherwise, the AACR general meeting in San Diego in April 2024 is the obvious occasion to get the word out.
Sorry BV, but I must disagree. It makes perfect sense to compare the ava6k dosing level to the straight dox 'equivalent'. The straight dox equivalent is the baseline. It is the number where we can compare benefits and side-effects to. We know that a dose of 209mg/m2 of straight dox would be near-lethal. We also know that a lot of straight dox never makes it to a tumour, or even into the body tissue, it is excreted from the system. And once we know the amount of dox in tumour biopsies from straight dox at a given dosing level, we will directly see what the amplification factor is for ava6k (i.e., how much more dox is in the tumour due to the targeting).
@Wiggly - yeah that is a great question. I don't know. A part of me says "how could they not?" But i don't know the protocol or ethics for obtaining biopsies.
Pivotal trials usually have a head-to-head comparison between the drug being tested and the standard of care. It is not a requirement, but it is usually requested by the FDA. However, there is also usually a 'get out' clause, meaning that if a patient is not responding to standard dox in this case, they can be moved over to the ava6k arm.
With that in mind, it is also not required that P2 makes it to the end. If, after a representative patient pool has been dosed in both the ava6k and dox arms, ava6k is performing statistically better than dox (which could be in the safety profile, efficacy, or both) the FDA can stop the trial and ask avacta to apply for approval.
I would also argue that it would be worthwhile to carry out a biopsy of a straight dox (75 mg/m2) patient to directly compare the amount of dox in the tumour between straight dox and ava6k.
@cj62 - in principle they could have reached the lifetime cumulative dose limit before they hit MTD. But once a cohort is dosed, and they don't find an MTD at that dose level, they can't find an MTD for that cohort in the future (i.e., the MTD will come at a higher dose).
@LLP - once a patient is dosed at a given level (say C3 level) they stay at that level for as long as they can continue to tolerate that dose or their cancer progresses (or in principle, until it goes away).
@icecool: you're right, for the Sept. 2022 results, they did not have a presentation or Q&A. However, they did have one for:
Spring 2023
Spring 2022
Fall 2021
Spring 2021
Fall 2020
Spring 2020
etc.
So, have a presentation and Q&A is not linked to new info. I wish it was, but it clearly isn't, unfortunately.
@Nanomat and icecool: this is literally what happens at every financial update and AGM. News is not scheduled around these events. And they always offer the opportunity for investors (or potential investors) to ask questions. And yes, I'm sure that 90% or more of the questions are the same from one event to the next (3 years ago all questions were about updates to the LFT and today they will all be on updates of ava6k trial).
Of course, there may be news dropped in the meantime, but as we have seen every six months for many years now, the financial updates are not events scheduled around news, or even opportunities used by the company to provide meaningful updates.
Thanks gje, great post! I was struck by this line, talking about previous attempts to use FAP: ". Those drugs that underwent clinical trials had limited success. FAP-targeting immunotherapy has demonstrated a nonselective recognition of FAP-reactive T cells on pluripotent bone marrow stem cells. It led to lethal bone marrow hypocellularity, necrosis, and cachexia."
As I recall a quote from AS in the spring of 2022, when referring to the pre-clinical data of ava6k: "Other companies have tried, and failed, to achieve this level of specificity [in targeting FAP]." And we know from C1-C5 that ava6k has an excellent safety profile. It seems that have, indeed, cracked this problem.
@PL: my understanding is that the box to check relates to the number of patients. And that is the difference between p1b and p2.
@lda: no it doesn't. mtd has no relation to how p1b/p2 are planned.
@pl: yes, i think that there is something to this. they won't skip p1b, but p1b is effectively a p2. if the signal of efficacy is clear (and from everything we have seen so far, this seems very likely) in p1b, then there can be "limited approval" by the fda after p1b. this means that p2 is still required, but that sales can commence and patients can begin to benefit. if p2 doesn't show the kind of expected benefits foreseen, the approval can be rescinded. a recent example of 'limited approval' is lartruvo, which was approved after p2 and sales commenced. in this case, the drug failed p3 so the approval was rescinded.
the approval for ava6k would be for sts. but here is the bigger question for me. can it also be used off-licence with limited approval? imagine you are a doctor that treats a fapa rich tumour type (e.g., breast cancer) that often is treated with dox. wouldn't you prescribe ava6k in this case? if i had breast cancer (or ovarian or pancreatic) i would be pretty ****ed off if i wasn't given the chance to benefit (no cardiotoxicity, little-to-no side effects, etc).
if you want a big example of recent off-licence drug prescriptions, see ozempic. this is a glp-1 analogue used initially by diabetics. it has been shown to be an effective weight loss drug, but (at least in the uk and europe) it has not been approved for weight loss yet. however, it is prescribed off-license for weight loss, and the the amount they sell as a 'weight-loss' drug dwarfs the market for diabetics.
yes, this is definitely speculation, but with solid examples backing it up. sts is a rare cancer (and even then with a large possible market), but things get exponentially more exciting when considering other fapa rich tumours that respond well to dox.
@Neut: it's a good question, and one that has been debated on here a few times. The question is whether the lifetime/cumulative dose limit is based on the amount of dox injected (in this case, as part of ava6k) or whether it is measured in the blood (to take into account ava6k's targeted nature). I asked this of FMcL at the AGM and she confirmed that it was measured in the blood. So, due to the fact that ava6k is much more targeted than straight dox, it is not restricted by the same limit.
Comparing the amount of dox seen in the blood in C1-C4 (given to us on the SD slides) to the amount of dox in the blood when given straight dox (both at 24 hours after infusion - the latter can be found in papers in the literature) it seems that there is ~5 times less dox in the blood (for the same effective dose) for ava6k than for straight dox. So, to first order, the lifetime cumulative threshold of dox will be reached at ~2500 mg/m2 (or 3700 mg/m2 of ava6k). None of the patients dosed so far will be anywhere near that level...so not something we need to worry about for the forseeable.
Ah the peace of the green box....
That Touk and Wyndy both posted after a 3 hour lull in posts on the BB. It is clear that their job is to generate posts. They simply say something controversial, something that they know people will respond to. How tedious.
@Moneysponge: No, if the effect (i.e., death) happens after the infectious phase (like in case of the coronavirus) then there is little or no selection pressure to become less deadly.
In retrospect, yes, the window for LFTs was quite short, so every day mattered. However, that was not a given, and in fact argued against by most scientists and governments. But viral mutations are random and chaotic, so there was always a possibility of it becoming less deadly. And we got lucky that it did.
https://www.politifact.com/factchecks/2021/dec/08/facebook-posts/viruses-and-other-pathogens-can-evolve-become-more/
It is difficult to know sometimes if posters are being intentionally provacative or are simply misinformed/mis-remembering what happened during the LFT period.
@Ianbt: In 2020/2021 the UK was using 10s of millions of covid LFTs per month. And this was just the UK, the USA was much more and testing was hugely common around Europe and Asia. The potential market for a cheap and accurate test was in the 10s to 100s of millions per month. It took longer than expected to finish the test (I'll grant that), but it was ready in January 2021. However, due to delays in getting it verified (largely outside Avacta's hands), it wasn't approved for sale until June 2021. At that time, there was still a very significant LFT market although it was only approved for businesses (i.e., with a health care professional present). Again, due to delays in government processing, it wasn't approved for home self-test until Dec. 22nd, 2021. Even at that time, the market for LFTs was still quite significant.
Around November 2021, the Omicron variant became the dominant variant in Europe and the world. Humanity got very lucky as this variant was significantly less deadly but outcompeted all the other variants. This was by no means a given that this would happen, i.e., look at smallpox, HIV and any number of other viruses that have not gotten less deadly with time. It was at this time, due to the decreasing severity of infection, that testing took a massive dive. There is no way that Avacta could have predicted this. As we know, the LFT didn't do particularly well with Omicron (although from everything i've read most other LFTs also performed much less well with Omicron, they simply didn't advertise this fact), but that was largely irrelevant as the need for testing dropped massively at this time.
Hence, the estimates provided by the company and by many posters on this board were reasonable and accurate given the information that we had at the time. The delays imposed by the UK government meant a delay of ~12 months or more, which did significantly affect the number of tests that Avacta could sell. Luckily, for humanity, the need for mass testing evaporated in late 2021/early 2022. This was unlucky for Avacta and us SHs from a monetary point of view.
Posted this on twatter last week, comparing dox market to that of ava6k.
2.7x - the amount of dox per cycle of treatment (if they dosed at C6 levels)
3x - three times the dose allowed (Avacta have stated that one of the goals is 2-3 times the number of cycles)
2x - the patient population (people above 65 and others with e.g., heart conditions)
2-10x - the cost of ava6k vs. dox, i.e., on-patent drug vs. generic. Typical values in the field of 5-10x...2x would be an extreme lower limit.
Total: ava6k would have expected sales of 32 - 160x more than straight dox for STS alone. And while it may take a couple years to take over the entire market, I think it would actually be relatively quick. Look at the sales of Lartruvo to see how fast it can rise, even with questionable efficacy. So whether the dox STS market is $1 or 2 billion doesn't matter much.
Remember STS is a rare cancer. Now, start using ava6k on breast cancer, lung, ovarian, pancreatic, etc, and the above numbers are dwarfed. Of course Avacta would have to demonstrate superior efficacy and/or safety to move into those tumour types over their standard of care. But dox was used as a first line against many of these tumour types until recently, so we know it works there. Take away the worst of the side effects and it's not hard to see ava6k becoming the standard of care for many of these tumour types in the not-too-distant future.
The first steps on this path will hopefully come in the next weeks/months, as soon as some initial efficacy data are shown.
I predict C6 finishing and C7 starting this week or next at 380 mg/m2.
@LDA - do you actually think that they would put out an RNS saying "We think MTD might be close." No company would announce a guess, they will announce it when it is seen/measured.
For cash flow and future financing, they had the AGM in June. How often do you want an update? I guess what you really want to know is what kind of deals they hope to do in the future. Again, no company would announce this.
As for the dx integration, in what sense? What info do you want here? let's just say "good". Each company kept their management in place, so there isn't much to 'integrate'. If you want to know if any new affimer based products are coming out soon, the answer is no. We were told at the AGM that it takes ~3 years to bring a new product to market.
It's summer, July and August are typically low news months.
@Thompi - nothing is official for P1b yet, but yes Avacta have mentioned in slides (and at the AGM) that it is possible/likely that they will be changing the dosing cycle from every 3 weeks to every 1 or 2.