Ryan Mee, CEO of Fulcrum Metals, reviews FY23 and progress on the Gold Tailings Hub in Canada. Watch the video here.
@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.
And £2M+ of options. do some basic research.
Yes, the C7 data should be remarkable. But they won't RNS the data. As we were told in the Q&A, they are holding data back in order to present the at a major oncology conference. One can only assume that they are holding back the best data, to maximise the chance of an oral presentation (as opposed to a poster presentation) as well as to make the largest possible splash in the community (if not the media).
From this perspective it is worth noting that they did not mention cardiotoxicity in the December presentation, which is note worthy as this is the limiting factor in using standard dox. Also no real discussion of quality of life, alopecia, or any comments on efficacy for patients in C6 or C7. It's going to be one hell of a presentation.
Timster - indeed, P1a now has two arms. Arm 1 is C1-C7. Arm 2 is the bi-weekly dosing. So no, P1a is not complete, but should be mid-year (if we believe that timeline...although I am quite surprised that the first cohort (all 3 patients) has started yet).
@Timster - why? They openly said that they held things back from the Dec. presentation in order to have 'new material' to present at upcoming conferences. Examples include case studies of C6 and C7 patients (where we expect the largest effects, both in terms of dose level and, C7, hopefully patients with less previous treatments), lack of cardiotoxicity (a major point that just happened to not be discussed in december), quality of life of the patients, detailed biospy data, etc. I think they already had more than enough for an oral presentation in December...and definitely enough by the early Feb. final deadline (and of course new data can be included after this point...it just won't be in the abstract).
Which is likely to be an ADC. Those are the best currently available approved therapies. Typically don't use a monarch to try out new (unapproved) therapies.
The Precision platform patent does not cover Affimers. Affimers are unrelated to Precision, two separate platforms.
@FS - If ava6k would take the standard route to market (standard FDA approval), it would be expected to gain approval in mid/late 2026. It would be this quick due because a Phase 3 is not required (pro-drug forms of approved drugs often don't need P3), making the upcoming Phase 2 'pivotal'. However, given the results so far, specifically the safety profile and early efficacy signals, in addition to the Orphan Drug Designation status, there is good reason to believe that ava6k would be a candidate for accelerate approval or breakthrough therapy status. In these cases, it could be brought to market (temporary FDA approval) much earlier, and would gain full FDA approval at the end of P2. This could happen at the end of arm 2 of the P1a study, which is expected in mid-2024.
As has been stated many times Hurst, what Novartis mean by precision is gene sequencing, nothing to do with Avacta's Precision. That is their focus, pretty much a 180 degrees away from Avacta's Precision (i.e., patient specific treatments based on their genes rather than a broad chemotherapy with general utility).
That's not to say that they wouldn't be potentially interested in Avacta's Precision in the future, but that is not their focus now.
@LDA - no, I can't imagine a FSTE 100 CEO starting that, but by the same token, I can't imagine a FTSE 100 (or Nasdaq listed company) stating that they have drastically reduced side effects of a potent chemotherapy, thereby allowing for 2-3x more doses, with clear efficacy signals in humans and that the drug was working much better than imagined possible, and then the stock price going down.
That is not the CEOs fault, that is the market behaving irrationally (i.e., traders controlling the market). Should Avacta get off AIM? Of course. However, the resources and time for moving exchanges are significant, and of course there are tradeoffs with the move (i.e., moving to a real exchange is not only sunlit uplands). Should deals be made? Of course, but negotiations take time and can be subject to events outside the control of Avacta.
@CTSFO - Avacta need to buy standard dox from somewhere in order to make ava6k. So the current producers of standard dox won't need to change their business model (or look to partner), as it seems likely that much more dox will need to be produced due to ava6k than is currently made. So the current makers are actually set for relatively big gains. All they need to due to strike a procurement deal with Avacta (or whoever Avacta partners with make ava6k).
@starbright - actually, biotech companies often/typically use conferences to announce major results. The reason is that the majors and press are present, so it’s a great forum to make a splash.
Of course, calling out any and all vaguely oncology focussed conference is pointless, so those posts should obviously be ignored. The difference here is the statement in the Q&A response that they have held back data explicitly to present at a major conference. The pre-eminent oncology conference is the AACR, coming up in April, which matches timescales.
@cemented - nope. As per the Q&A responses, data was held back to enable presentation at a major oncology conference. Likely AACR in early april.
HG4- it was in the Q&A answers.
Bella - dox is a generic drug, made by multiple companies, hence this will not be a limiting factor (i.e., a manufacturer who 'calls the shots'). Most likely, as in any drug production, multiple dox manufacturers will be contracted to provide that drug as part of ava6k, so as not to have a single point of failure. Now, who makes ava6k is anyone's guess. It almost certainly won't be Avacta. But looking at currect dox manufacturers is unlikely to play a major role in the calculus.
Also, more frequent dosing of dox is an age old idea, so this was almost always certainly on the cards. This wasn't a new idea by a major. Take away or reduce the side effects, and it was always the goal to reduce the time between dosings. It has been shown multiple times in clinical trials, that more frequent dosing leads to better results. The problem is simply that at the same time, there is more damage to the body (white blood cell counts specifically and knock on effects) which means that on balance, the patient is worse off.
The completion of a cohort is a fairly nebulous concept. There may be an official end (as LL suggests, which seems reasonable to me), but little changes at this point. The patients still get dosed, still get monitored, etc. after this point.
And to be a pedant (sorry BV, I beat you to it), P1a ends with the bi-weekly study sends - i.e., arm 2, not when c7 completes.
Given that nothing changes at the official end of c7, I don't expect to get an RNS on this. We definitely won't see any data from c6 or c7 until the big release presentation.