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Perhaps. But they would need some of the doctors running the trial to also come out front and center and really hype the results. Also, when it comes to making a big splash in the media, you only really get one big go. They don't do it in pieces...which I guess is why Avacta are saving their ammo.

I agree gadgie, that could drop anytime now. And another one, the next preCISION drug selected for pre-clinical IND enabling studies.

Thanks MrR. I'm afraid I don't know. I can see a case being made where the first 4 cohorts (the planned ones) followed a more or less set sequence in order to plot out the concentration (blood, urine, biopsies when taken) and side effects. Perhaps with this data in hand, they are willing to take a bit of a risk and escalate significantly to trying to find an MTD (or at least a much higher tolerated dose if an MTD can't be found) and try to find it with one or 2 more cohorts. If they go above the 40 mg/m2 increase, it seems clear that this is what they will be trying to do. On the other hand, clinicians are a conservative bunch (perhaps not surprisingly since they may lose their reputations and/or licenses if they are deemed to have acted too boldly). For me, this will be the next big news (hopefully tomorrow as Timster has divinely predicted) and may give us some good insight.

@Muck, I absolutely agree. And Fiona has also hinted at this...perhaps you don't want a dose near MTD, perhaps a dose that doesn't cause any significant side effects but can be given for longer/more cycles is the best way to go.

One question that I would like to see addressed is whether P1B needs to keep to the standard 3 week chemo regimen. Was this set up to give the body a chance to recover (i.e., to try to heal the healthy tissue destroyed by the chemo) or was this set as the optimal attack on the cancer. I've always assumed the former....

This is a good question, what will the next dose be? So far, it's been in 40 mg/m2 steps (80, 120, 160 and 200 mg/m2), so it stands to reason that the next will be 240 mg/m2. That's all well and good, except that the predicted MTD, based on the mice models is something like 4x the standard dose (the ava6k dose was 6x higher than the dox dose in mice, but one needs to correct for the weight difference (0.67), which brings it down to 4x). C1 was dosed at the equivalent of 54 mg/m2 (which was 90% of the standard dose, which would be 60 mg/m2). 4x 60 mg/m2 = 240 mg/m2 of dox or ~360 mg/m2 of ava6k.

So if we would keep going in 40 mg/m2 steps, it would take another 4 cohorts to reach this level. Also, as noted by Alan last April, systemic levels of FAPalpha are much lower in humans than in mice. So the MTD ratio (ava6k to dox) may much be much higher in humans than in mice. In this case, MTD would never be realistically reached in a P1a trial (i.e., you may need >10-20 cohorots).

It will be interesting to see if they keep going in 40 mg/m2 steps (which, given the above, is unlikely to reach an MTD), or if they kick it up a notch and start going in 60 or 80 mg/m2 steps.

Like others have said today, I expect an RNS in the next few sessions stating the next dosing level. Will be interesting to see, and may give the game away regarding the level of ava6k tolerated by humans. If they kick up the dosing level, this will be an extremely bullish sign. If they stick to another 40 mg/m2 increase, it may reflect that they expect MTD to be close, or may just reflect the conservativeness of the committee.

Thanks for the link ST. This is also where I inferred that the dox cumulative lifetime dosage would not be a limiting factor for ava6k. There has been a lot of debate on this subject on the BB, whether they can keep dosing patients (assuming they see some positive effects and few or no side effects) past the nominal dox cumulative lifetime dose, or if they need to stop. I argue what Alan just said (in the link) is that they can keep going. For that they may use the amount of dox observed in the blood plasma (i.e., how much makes it to the system in general) and not how much was injected into the patients as ava6k.

Think back to those handful of cancer treatment stories that were covered in late December and early January. They all had that personal side to the story. The guy who had terminal bowel cancer (I think it was bowel...) and given less than a year to live, but then got this new therapy, and has fully recovered. That was all over the news, regardless of the fact that that type of therapy will only work on a very small subset of cancer patients. So the big picture is less important than the personal aspect.

Now, I hope and expect that Avacta's ongoing trial already has, or will shortly have, a few such stories. Hopefully they will be shared (is science day too optimistic?) and then the press will be all over that. More press means more recognition, meaning new investors, both big and small. My belief is that when this does it the main press, that is when the rerate will happen.

To make it into the main press, there must be some statement about efficacy. Something like a case or two of terminal patients making a recovery, or some statistics about tumor reduction. To the outside world this sounds like just a technical achievement, rather than the massive revolution in chemo that it is.

Now that the (preliminary) data have been released, I argue that the potential for announcing licensing deals has increased significantly.

From Question 4 (Q4) in investor presentation: "There is a strong level of interest in the preCISION platform and this will be driven further by the Phase 1a data....it is the clinical data that will be key to future significant licensing deals." (https://twitter.com/RAH00084/status/1613822406551912454/photo/1)

We are 12 months in to ava3996 pre-clinical IND enabling studies (https://www.lse.co.uk/rns/AVCT/second-precision-pro-drug-candidate-selected-nf1gtw1ehjqcqyh.html). We haven't heard a thing on this since they announced it. Results from this should be ready in the next 1-2 months. Is this the drug that Avacta plan to license out (thought so by many)? Or will be it a preCISION version of an existing, propriatary drug?

But the most interesting part of licensing out further drugs, like ava3996, is that they are already significantly de-risked. It's the same chemistry as ava6k. So if ava6k cleaves, so will the others. The leaving groups should be very similar (or even identical), so there should be little safety risk there as well. For ava3996, they also already have loads of results of animal models, further showing that it cleaves just like ava6k (assuming it does). So I would expect any licensing deal to not represent typical 'pre-clinical' asset value estimations, but something closer to clinical stage values...perhaps something in between. As Alan and others in Avacta keep mentioning, successful ava6k results 'confirms the potential' for the entire pipeline.

Now that the results are public (with hopefully much more detail to be presented at the Feb. science day), deals and agreements are much more likely. Should be an exciting few weeks to months.

I believe that there were two examples quoted recently (perhaps by RAH, Energy or Tom?) of large deals coming just weeks after initial (phase 1) data were released...but I can't seem to find the references. Anyone remember this?

90% of solid tumors are enhanced in FAP, a much larger percentage than dox is used for currently. And yes, there will certainly need to be studies done on ava6k in combination with other treatments. However, note that many combination treatments are done in order to avoid toxicities leading to death or near-death. i.e., you give two chemotherapies that have two different types of toxicities (e.g., heart vs. neural degeneracy). If ava6k has significantly less toxicity than standard dox and is also more powerful (as found in the animal models) some of the combo treatments may not be needed.

Excellent point BV...not necessarily a delay, but indeed that changes to the protocol could be very helpful/important based on what they've seen in P1a. Increased frequency and/or increased maximum dosage (back to the old argument about whether the max dox equivalent dosage is based on level in blood plasma or given amount) could be extremely beneficial (as these values were based on tolerance of traditional chemotherapy).

Amusing indeed. From what I can tell from the Conference website, this is a conference many focussed on connecting investors (and institutions) and companies. i.e., not a scientific conference. As such, I would find it very strange if Avacta used this opportunity to release their P1a data. While of course investors would be very interested (and it is likely to cause a major splash), the P1a results are a science outcome and will be aimed (initially) at the science community. At least that is what I've seen in other pharma companies announcing results at conferences.

MrR, can you give an estimate of how many there are normally? I assume yesterday was the same? Perhaps Timster's right on this.

Darpins seem to have some significant problems associated with them:
https://www.evaluate.com/vantage/articles/news/deals/bad-day-molecular-partners

Interesting as there doesn't seem to have been a 'reason' for this article. i.e., no new results or claims, just a general advertisement for the company. Strange as their share price is dropping like a rock these past few months.

I thought that it was linked to the Science Day, hence will come in Feb now.

I think that anything related to Precision (including TMAC, ava3996 and further pipeline development) will need to wait until after the ava6k P1a update. But after that update comes, I expect a flood of updates over the following few weeks. After ava6k update, we may finally hear more about ava3996 and hopefully even an announcement that the next candidate is moving into pre-clinical IND enabling studies. Presumably a license deal (for ava3996 or maybe a specific deal for a patented drug) will follow the update. Also a TMAC update; would be amazing to see that move into pre-clinical studies...although it's not clear to me what the potential timeline there is.

But then you always have the wild cards. Diagnostics update or Affixyell, or an unrelated affimer licence deal. Or even a therapeutic update, brining ava028 into pre-clinical studies. This is part of the affimer oncology, separate from Precision.

The last couple M&A that we've discussed on this board happened 2-3 weeks after important clinical studies were released, hence the period between the update and the Science day should be an exciting time.

For what it's worth, I do not expect further dose escalations, rather the update on ava6k progress will present a simplified summary of the P1a results and an announcement that P1b will be starting soon.

Hola BuenaVista, thanks for the question. I was blown away when I first heard about Crispr/Cas9, the potential there is phenomenal. I originally bought in to Editas, Crispr, Intellia and Caribou, as it was difficult for me to differentiate between the companies, in the sense of which one(s) were likely to be the field leaders in 5 or 10 years. Editas and Caribou have been disappointing, but Crispr and Intellia have really demonstrated the promise of a truly disruptive platform. If you are interested in the science behind Crispr, have a read of "A Crack in Creation" by one of the discoverers, Jennifer Doudna.

Honestly, I found it difficult to judge the Beam pipeline and how likely they are to be disruptive. I still look at them from time to time, but find their investor presentations to be frustrating.

My other big US pharma play was Moderna. Again, amazing technology (mRNA) that I can easily see becoming a staple in medical treatments in the next 10-15 years.

Like Avacta, they all are developing a new technology that has a real chance of disrupting medicine in the near to medium future. (ps. I try to have a relatively balanced portfolio with a majority of traditional slow growth picks, and ~30% in somewhat more risky investments with the potential for disruption.)

@Livedata: No, that is not typically how M&A works in pre-revenue generating bio-pharma. For example, Pfizer paid x3 the mcap for Trillium Therapeutics this year, which was a Phase 1/2 oncology company. Trillium had some good programmes of checkpoint inhibitors for blood cancers, but I think compared to the potential market of drastically reduced side-effect chemotherapies, they were small fry.

Hi Nanomat, from what I can tell, Capiversatib has a completely different mechanism of action from ava6k. Capiversatib is a protein inhibitor, meaning it bonds (fits into) the protein and effectively makes it inactive. Ava6k uses a cancer specific enzyme (or at least significantly upregulated) to break the Precision bond, thereby releasing dox into the tumour environment directly. So other than using general chemistry, the likelihood or failure of either drug has little or no relevance to the other.

But of course this is great news for those with breast cancer. Hopefully ava6k does even better.

@Energy. Thanks! Indeed a single vaccine the demonstrated that the underlying technology worked. Sound familiar?