Member Info for jive_turkey

@GoSushi - not sure. But my guess is that we could use the Keytruda Melenoma study as an example...so 150-200 or so?

@GoSushi - that's true, a Phase 1 study with n=173 patients.

@GoSushi - Avacta have mentioned that they are in direct discussions with the FDA currently and that the results of these discussions will be made public 'mid-year', i.e., when the Q2W trials ends. Approval at this stage (it would only be limited approval and further trials would be required) would be a pretty amazing feat, but if the results continue to be stellar it is possible (significantly improved efficacy and reduced side effects). To be fair, it is more likely that these conversations are about trial design in order to obtain approval after the P2 trial. But one can hope.

@AVCT - The disadvantages would be giving a drug to patients (before it is fully proven with long trials and hundreds of patients) that isn't as effective as the standard of care, or has some particularly bad side effect that hasn't been discovered so far in the trial due to low numbers. While the chances are low of this (the data so far are pretty clear about the advantages of ava6k), this is why the FDA (and medical community) go slow and systematically.

Earliest: Sept 2024 (at the end of Q2W)

Latest (most likely): end of P2, so sometime in 2026.

(assuming the stellar results continue)

My guess is August. And like the Q3W trial, the more dose escalations they go through, the larger the potential benefit to patients, but the longer it will take. Hopefully they make it to the C6 dose level.

Exactly my think PL 👍

Yes, we have been told that Avacta are in active discussions with the FDA and that Avacta will not be able to comment on the discussions until mid-2024. Two things to note: 1) it is not common for a company to be in 'active discussions' during a clinical trial (i.e., normally once approved by the FDA the company just gets on with the trial) which implies that there is something that needs discussion, of which breakthrough status and/or accelerated approval requirements are possibilities. And 2) why mid-2024? That is when the 2QW dosing trial is predicted to end. Hence, it will be after 2QW that the results of the discussions might be released.

What do you mean York? Avacta already have orphan drug designation for av6k.

It will be a subtype of STS.

Great stuff Rambo!

@Taverham and Largo - no, this is standard practice in biotech. New results are often released at conferences and then released to the market afterwards. Sometimes after the conference entirely, but in our case it will just be after the poster presentation on Tuesday. So we will get a copy of the poster along with CC's explainer video Wed morning (the poster could conceivably be released on Tuesday evening UK time, but more likely Wed).

No, poster presentation on Tuesday at the conference. Poster and data will be released to us on Wed.

Agreed LL - it's a tough decision and critically dependent on what the offers (for ava6k or 3996 or other Precision drugs) are for and for how much (upfront and percentages).

A good comparison to ava3996 - BMS paid $100M upfront for a "phase-1 ready ADC" (i.e., end of preclinical) for an ADC from Orum Therapeutics for acute myeloid leukemia which is a relatively rare form of cancer. And ava3996 is meant to be "tumour agnostic". So that's the ballpark we're playing in.

@GoSushi - that has been addressed multiple times. The Phase 2 will be pivotal (assuming that it meets all primary and secondary endpoints), meaning that it can be approved based on the results. Phase 3 will still be required (as in all drugs) but that can take place while the drug is on the market.

And since their valuation has a generic 'chance of success' of ava6k that is only tied to the clinical stage the asset is in (i.e., Phase 1a gets a 10% chance of success) it will likely jump by a factor of 2 or 3 when we enter P1b/P2.

For me the major difference (as Avacta's technology appears to have a much larger longer term potential) is that Profound is a US company (not listed) and when it raised cash in Feb, it raised $130m, not a token sum of $30m. This type of raise (as it had done previously too) has allowed it to take three assets into the clinic in rapid succession. If it was for being perennially running on fumes, Avacta should have brought ava3996 and likely an affimer into clinical trials already.

Raising money in the UK is a suckers game, the markets can't and won't appreciate young biotechs.

For those that say "it's a difficult market to raise money in", I'll respond by saying only in the UK. US biotechs are surging and seemingly not finding it difficult to find funds.

Some will bring up the Dx acquisitions. Obviously, I would be against those as well. But from what I hear, those were a requirement of the raise at the time.

Yes, I'm upset about the 50p placing for pennies and paying back the loan is a kick in the butt. But the real tragedy is that the rest of the pipeline (ava3996, the rest of Precision affimers, and TMAC) is so delayed due to the lack of funds. These have all been pushed 18+ months behind, at least.

That's just a page from Myles McNulty's excellent research note from last year.

@AVCT - That seems very unlikely. Given that AVA7000 and 7500 were developed for Precision (FAP activated). Also, sucrose is not up-regulated in tumours as far as I know.

This could be simply part of the detailed study work on the two drugs. For example, sucrose is used in many staining techniques to study the effects of drugs on cell lines. Just one possibility of many.

But you are right that even through FAP-rich tumors make up more than 80% of solid tumours, and solid tumours make up the vast majority of cancers, it doesn't make a lot of sense to keep making new prodrugs along this line. On the one hand, we know that each chemo, with its own mechanism of action, is better at attacking certain tumours (e.g., dox goes after tumours that are reproducing). So in principle, it could make sense to have multiple Precision drugs. On the other hand, having a tumour agnostic (e.g., ava3996) treatment, which would also likely include very potent warheads, would likely outperform the individual Prodrugs of Precision. Hence, I am sure that Avacta are thinking long and hard about their strategy of licensing Precision and further Precision candidates. No point bringing multiple drugs to market that end up eating each others market share.

Yep. https://aimchaos.com/wp-content/uploads/2023/02/avacta-group-validation-of-precision.pdf

This is from Myles McNulty's research note from 2023.