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No, the bi-weekly trial (ie., a shorter dosing regimen) was always part of the plan. The three weekly dosing was always a limitation with dox. The goal of removing the side effects and therefore allowing dosing more often was a clear goal from the beginning. The postmarking trial (i.e., continuing the trial after approval) was also always going to happen.

That said, it is also clear that Avacta are in contact with the FDA and accelerated approval is definitely the goal. The Orphan Drug designation means that the FDA can and will provide advice on the trial design (with an eye for accelerated approval). The bi-weekly will provide more data, and the expectation is that this will also greatly improve the efficacy (ava6k vs. dox). This will help get approval in the long term.

The 40 day news blackout period that is being discussed here is supposedly a rule based on US investors in a placing (specifically that the Investor/Fund can't be identified nor the amount invested). I'm not an expert, but i've done some searching on the interwebs, and I cannot find any reference to this. There is a 'blackout period' which is about insider trading (which doesn't apply in this case) and there is a 40 day "quiet period" but this refers to an IPO. So it's not clear if such a news blackout is real. Does anyone have a link/reference to this?

No, what is shows is that they have to balance competing factors. Buy too little (as some are endlessly repeating) and it shows that they don't have confidence in the company. Buy too much (as they have also been accused of by others) and people think that they are taking advantage of the low share price.

@Mustang - he also said that they are generalist investors who don't have experts look at the data/science.

That was one of the original cancer types that were floated as potential targets for ava6k and so far 8 pancreatic cancer patients have been treated in P1a.

@LLP and others - Sorry, maybe I'm being thick here, but I'm missing something. So the first placing was for £25.7 million. And all of those need to be issued before 8am on March 11th (monday). Ok great. And the REX offer is for 10.9m shares. This needs to be approved on the 18th.

So there will only be 10.9m shares offered after the 18th..where does 34.8m number come from?

Also Mologic changed it’s name to Global Access Diagnostics in 2021. This may be an old article that has been revived by the publication and just given a new date. Bummer.

I’m a bit confused though, Avacta got ISO13485 certification in 2021…

Hi BV, yes, I also don't fully understand the optional spacer. I looked into this a bit, and this seems 'ok' for ava3996. i.e., after it cleaves the 'spacer' affects the kinetics, but doesn't interfere with the warhead...i.e., the killing mechanism (the business end) is on the other side and isn't affected by the spacer. But of course, this can't be used for ava6k or anything else where you want the cleaved molecule to be exactly the same warhead before Precision.

But I wonder if this is going to be relevant to 'new' treatments like MMAEs? These are never given as a stand alone (unlike dox), they are always part of the ADC. So presumably, even if Precision cleaved the exact same form of an MMAE it would still be a 'novel molecule' because it will have never existed on its own before.

All the standard chemos that Avacta have listed then can't use the spacer, but since they are already used as stand alones, their kinetics is likely to be ok. It is only for new molecules (i.e., ava2727d) where their kinetics may need to be tweaked. And if this spacer can tweak them without changing the business end, then all is well.

Like others, I'm disappointed that the AACR presentation will be a poster instead of an oral slot. It is indeed rare for Phase 1 results to get an oral slot, but it's not unheard of, and I thought (compared to oral presentations last year) that the results presented in December would have been good enough. Whether it was just the (non-hyped) way that the abstract was written, or if the competition was strong, remains to be seen (remember that there are only a finite number of oral slots so competition for them is fierce).

However, I've seen some posts saying that the removal of "Paradigm Shift" from the title is a bad thing, that perhaps the results aren't as good as we were led to believe. This is nonsense. This is a scientific presentation. Any company/clinician that would put "Paradigm Shift" in the title of a AACR presentation would simply be laughed at as wholly unprofessional.

Yes, the wording has changed from the December presentation, but that is simply because the audience is different. In December they were speaking to investors (non-specialists) and at the AACR they are speaking to scientists (experts).

If AS (and others) don't buy enough (despite having £5m+ of options) then it shows a lack of confidence in the company. If they buy too much they are profiteering from the low share price. People have been whinging both ways this week. Funny that.

I sincerely hope that they don't wait until ava6k approval before licensing out Precision for other drugs. Yes, it will be faster to go into and through the clinic compared to entirely novel drugs, but we'd still be looking at 1 year+ for preclinical, and 2+ years for the clinic in the best possible cases. And if it is a novel drug being attached (i.e., ava3996 compared to ava6k) then you have to add on a P3 which will be a further 1-2+ years. Hence, this would be a very poor model. The sooner they license it out, the sooner others can begin their work.

Of course it makes sense to take ava6k into the clinic and prove the mechanism of action before licensing out Precision. Proof of concept is worth a lot as it has been massively derisked. But there is little value to be added to Precision by advancing ava6k further. Of course, there is a lot of value to be added to ava6k (for a partner) with each new patient dosed, so the further they take it, the better ava6k gets. But that is for that specific drug, not Precision in general.

Thanks for the reply 👍.

@nysize - i agree.

You called it right and clearly had some prior knowledge of the placing. You also mentioned that we should be looking for "messaging" around this, so you had some insight into the bigger picture. But from what I can tell, there is little or no "messaging" in the RNS, i.e., no bigger picture that would help explain this. Can you tell us what kind of message you were expecting? Or do you know the reason behind this?

There are some that say that the Dx acquisitions were a requirement of the Heights loan (which makes sense to me as no one would spend money on Dx given the stage that Tx is at). Ok. But why raise now (at 50p) when it could have been 120p+ in November? Some say it is just a bridge to a big LD or TO, but that doesn't make much sense to me, given that Avacta have £15m+ in the bank, which if they tighten their belts could easily see them through 2024.

I fully understand that we investors don't have all the info, and that the BoD needs to make decisions and that often decisions that appear strange to us, have a rational explanation once all the info is known. But I have to admit that I'm struggling here.

@LDA - no, "Read out of two-weekly and three-weekly dose escalation study data in late Q2 2024;" So they still expect to finish Arm 2 before July 2024. But I agree, this the wording in other parts add confusion.

@D-Geeman - yes, that is certainly a possibility. Hopefully we get more insight on this from the company over the next few months.

@DTW - yes, very good point. There are multiple defense mechanisms within tumours. The stroma indeed can play an important role, so hitting the stroma (in addition to the tumour cells) is a big plus for ava6k. Another mechanism is in the tumour cells directly. They can develop internal pumps which removes dox from the cell even after the dox gets inside. In both cases, hitting the tumour + stroma with a high (and rapidly repeated...say every 2 weeks ;) dose may stop resistance from being developed.

@B2HS2L - Good question. There are two schools of thought on this. The first, which is the one you mention, that using ava6k at a relatively low dose could greatly extend lives by keeping the tumour in check (not growing). Based on what we've seen so far in the data, for STS patients this could triple or more their life expectancy (with an excellent quality of life given the low side effects expected). The worry on this is that the tumour(s) may develop resistance mechanisms, meaning that dox would no longer be effective. The second school of thought is that in order to avoid the development of dox resistance, a high dose of ava6k may be preferred. Effectively, nuke the tumours and accept some side effects.

Avacta have hinted both ways in the past, so I think that the best treatment programme is still to be determined. But as CTSFO has rightly pointed out, combining ava6k with other therapies may amplify the benefits of both.

I agree Ice. The two week dosing arm is an excellent chance to target STS *and* non-STS tumours, which if the results are good for e.g., pancreatic, ovarian, brest, etc, could lead to multiple P2 trials starting soon after the STS P2 (with the help of a partner of course).

@CTSFO - yes, I think you're right. It should be noted that many previous studies have shown that dosing dox more often (i.e., every 2 weeks compared to every 3 weeks) results in a higher efficacy against cancer. However, the main drawback is that dox is also killing healthy cells in the body, specifically white blood cells. So the three week dosing schedule is a compromise in killing the tumour while allowing the body time to recover. But it also gives the tumour time to recover.

So it has been a long stated goal for dox (and other chemotherapies) that if the side effects can be lessened, then a more rapid dosing schedule will lead to better outcomes. Avacta had to start with a 3 week dosing schedule because they had to prove the safety of the drug. Now that that is proved they can go on to a 2 week schedule. This was likely always the goal (as we've seen in presentations the past few years) and it can now safely be done.