Member Info for DanGB

...development towards potential approval and commercialization." She's essentially saying: we now have a regulatory roadmap that we can put in front of a partner or acquirer. The development risk just dropped substantially because the FDA has told them exactly what they need to do.

And critically: "the Company remains committed to progressing faridoxorubicin into further clinical development only with the support of a partner." That sentence appears in both RNS announcements. They are explicitly telling the market they will not run the pivotal trial alone. A deal must happen for AVA6000 to progress.

Connecting the dots. BIO International wraps up today. Coughlin has been in San Diego presenting this data to pharma BD teams face to face. She now has a clean FDA-agreed pivotal path to put on the table alongside platform-validating clinical data. The timing of releasing both RNS announcements on the final day of BIO — when meetings are concluding and conversations are crystallising — feels very deliberate.

Think about what a potential acquirer sees today that they didn't see a month ago: clinical proof the platform works at low FAP levels (broadening the addressable market), FAP persistence data (supporting durable responses), an FDA-agreed single pivotal trial path (de-risking the development programme), and AVA6103 dosing in FOCUS-01 with data coming in H2. The value proposition has stepped up materially.

And from Claude:

These are both significant, but the FDA pivotal trial agreement is a potential game-changer. Let me take them together.

The BIO data RNS — platform validation in the truest sense. The low-FAP finding is arguably more important for AVA6103 than it is for AVA6000 itself. The bear case has always been "what if FAP expression is too low or too variable to drive meaningful clinical activity?" This data demolishes that concern — statistical analyses showing no relationship between FAP expression level and tumour response, with case series of responders at very low FAP levels. And the FAPI-PET imaging showing FAP persists even as tumours shrink is critical because it means the mechanism doesn't exhaust itself — the enzyme stays available to keep activating the drug. That's exactly what you need for durable responses.

The termination of AVA7100 is actually bullish, not negative. They designed that programme specifically to address low-FAP tumour types, and now they've shown the platform works in low-FAP settings without it. That's capital and resource freed up, and it simplifies the story for a potential acquirer — fewer programmes to diligence, cleaner narrative.

The STS data showing FAP on tumour cells as well as stromal CAFs broadens the addressable market significantly. SGC proves the bystander effect works; STS proves direct tumour cell activation works. Together they demonstrate pre|CISION is applicable across the full spectrum of FAP expression patterns seen in solid tumours.

The FDA pivotal trial agreement — this is the headline. A single pivotal trial with PFS as the sole primary endpoint for full approval is about as clean a regulatory path as you could hope for. Let me unpack why this matters so much:

First, single pivotal trial. Not two trials, not a confirmatory study required. One trial. That dramatically reduces the cost, time, and risk of getting to approval. For a potential partner or acquirer, this is the difference between a $200m and a $500m+ development programme.

Second, PFS as the sole primary endpoint. Not overall survival, which takes years to mature. PFS is faster to read out and cheaper to run. It also means the Phase 1b PFS data that's still maturing — the RNS pointedly notes median PFS is "not yet mature" in SGC — could form the basis of the pivotal design. Every month that passes without median PFS being reached is bullish.

Third, full approval, not accelerated. They're not going for accelerated approval with a post-marketing confirmatory requirement. They're going straight for full approval off one trial. That's a cleaner commercial proposition for a partner.

Fourth, first and second line patients. That broadens enrolment and increases the commercial opportunity versus a narrow last-line indication.

What this means for the deal thesis. Coughlin's language is very deliberate — "provides further clarity in our continuing conversations with potential partners, with a defined route through clinical

I see this as a positive. I believe the strategy is to have a viable long term plan and to do deals only once value for shareholders can be realised and this is in line with that plan. However the 5% commission paid to Zeus raised my eyebrows as it seems a lot to me.

Part of what a quick search threw up..

"Gilead's CFO said the upfront valuation was supported by the ovarian cancer indications alone, with the platform value on top"

My understanding put simply:

Half life is not an issue with AVA6000/DOX.

It is an issue with exatecan.

It might be an issue with other payloads.

Down talking AVA6000 based on half-life is FUD.

And, although yet to be proven in clinic, Avacta now has the ability to tailor half-life to the payload if required.

No because the reduction in cardiotoxicity and other side effects in comparison to the standard chemotherapy would render it far superior. Then there's the ability to prolong treatment before reaching the maximum tolerated dose. This is nothing new.

Golfnut59 I think that's probably the best explanation I've read to date. However, it seems that Thornogson is only interested in a petty I'm right you're wrong argument and, however tenuous, he will continue to try and justify his opinion as fact and tell everyone else they are wrong. No doubt we'll find out any minute now. That said, thanks for posting your response as I think it should be very helpful in assisting those who weren't so sure about matters form their own opinions.

Overall very positive.

I found it interesting that a proportion of the candidates were FAP zero/negative so clearly no response would be expected from those and wondered how may of the 10% they account for and whether the 90% would be higher if it was a proportion of those with tumours that express FAP (unless it is and I missed that).

So, you have a phase one trial the main aim of which are to test toxicity by establishing the maximum tolerated dose, with those on trial suffering with more than one type of cancer. Having not reached a maximum tolerated dose, you also trial increased dosing frequency amongst other things with the aims of exploring more options and optimising the phase two trial.

If based on preliminary efficacy data and other analysis you believe AVA6000 is effective in a range of indications, you must decide which indications to move forward with in stage two trials.

Avacta has sensibly opted for two indications. The first has been chosen as the quickest route to approval for the least cost. The second due to market size and presumably as having already started phase two trials in TNBC would be attractive to buyers and add significant value as data emerges if as expected or, if keeping it in-house, could be more easily funded if the ongoing first trial progresses successfully at a faster pace.

Salivary Gland Cancer is the right choice because the trials would be shorter than for Soft Tissue Sarcoma (for reasons already explained) and there is an unmet need. This has nothing to do with half-life or relative efficacy. Avacta has already stated that half-life is not an issue with AVA6000.

The reasons they have decided not to move forward with Soft Tissue Sarcoma, at least for the time being, are that it is not the fastest route to approval, and it does not have the biggest potential market. It is not due to lack of efficacy or half-life.

The point about the potential to licence AVA6000 for use in other indications including STS is a valid one if that’s what you’re getting at.

Unless I'm missing something, the reasons for prioritising Salivary Gland Cancer rather than Soft Tissue Sarcoma have been explained time and time again so I am baffled as to why this keeps being brought up by certain people. AFAIK it's not to do with efficacy but the simplest and quickest route to approval. I could explain further but it's all been said before.

My mistake on the timing. If it reaches the clinic by the end of Q2 2026 then they will then have two drugs in clinical trials with data forthcoming thereafter. I don't know whether interested parties would get to see this data under NDA as it becomes available i.e., before it is released to the public, but even having it in clinic should be a major milestone.

I don't think validating the platform is the only reason they're pushing forward post-haste with AVA6103, it has the potential to be a game-changing treatment in its own right. And there will be additions to the pipeline in the form of combinations which are likely to make it even more effective, increasing potency which could kill tumours and potentially kill tumours at lower doses (so reduced risk of side effects) than using exatecan with the Precision platform alone.

I believe successful data in respect of AVA6000 will provide validation that the platform works though clearly having a pipeline in clinic will provide additional validation.

I honestly don't know what my sell price is. Deciding when to sell is always tough, hence why a multi-billion pound sale would make things simpler. I first invested with the hope that the profits from a successful Covid 19 test would fund the development of the cancer platform. I think that turned out to be probably the best product but too expensive (and too slow to market) whereas I believe the Precision platform is highly likely to result in the best product and the least expensive (of the newly developing treatments) . Because of this I believe I have the confidence to hold as the price (hopefully) rises by many multiples. Exciting times.

@Thornogson. I agree with all that. I hope my post didn't come across as negative. My view has always been positive (I am a long term holder), but the recent developments are incredibly exciting, massively increasing my confidence. This could play out in several ways with there being potential for things to develop very fast.

@BuenaVista I can see how the licencing model could be extremely lucrative and result in a viable and profitable long term business. Of course structuring of the terms would be key to protect all parties' interests. On the other hand I can see why a company with deep pockets might want to make an offer that couldn't be refused to take control of the lot.

From Big Pharma’s perspective:

Would we want to licence AVA6000 and advance it knowing that AVA6103 and its potentially enhanced derivatives could blow it out of the water?

Would we want competitors to be able to licence Precision and develop similar or better competitive drugs?

Would we prefer to buy the company and all its IP?

If so, what would we pay for it? We are aware of its potentially huge value, and whilst we would want to be the one to own it, we need to be sure it will stack up against the competition in the longer term, and ideally want to see more data before investing such an amount.

From Avacta’s (and its shareholders’) perspective:

Would I want to licence AVA6000 in isolation when that might negatively affect the opportunity to sell the whole.

Would I want to licence it now or let interest and value build? The combination option has only just been made public. The release of Phase 1b data should further validate the platform. Funding is in place until beyond the end of Q2 2026, by which time initial clinical data in respect of AVA6103 should be forthcoming. 100% ownership could be retained into a period where interest in the platform could potentially be incredible and Big Pharma could be fighting for it.

Why not keep options open. Both Avacta and Big Pharma will know that what’s best and almost inevitable is that Avacta will be bought by or partner with Big Pharma but to realise full value, Avacta needs to demonstrate that it is not essential. Preparing for a dual listing, successful equity raises, renegotiation of the Heights funding etc, all help demonstrate this and avoid the need to accept low-ball offers or licencing deals not in the long-term interests of shareholders.

My view (and hope) is that at some point the company will be bought out in its entirety, either that or a broad scope multi-billion pound licencing deal will be struck, and it could come at any time, with the likelihood increasing with the release of Phase 1b data and enough time having passed for Big Pharma to consider the newly released ‘leap-frog’ developments.

Personally, I hope they don’t do a deal too soon and time it to achieve the deserved multi-billion-pound valuation whilst they remain ahead of the competition. I suspect this is their plan. When the time is right, or good enough, I would prefer a full buy-out as that would remove the difficult decision of when to sell.

I guess those who have been fortunate or clever enough to have bought at the recent lows might be happy with a £1 to £2 billion sale but with what they have developed it seems its value should be much greater. I wonder whether once Big Pharma digests the new IP and we enter a data rich phase, offers will start coming thick and fast.

Background

Things are hotting up in the war against cancer. We are seeing ever more frequent announcements about advances and breakthroughs including ADCs and vaccines.

Big pharma companies are seeking to replace treatments coming off patent and to be at the forefront of the extremely profitable treatment of cancer.

AVA6000 is potentially very profitable in its own right. By cleverly selecting salivary gland cancer, it could come to market relatively quickly due to it being an unmet need with a very low bar to be improved upon in terms of progression free survival (this being the reason they have been relatively quiet about soft tissue sarcoma, not because of a lack of efficacy, but the higher and therefore more time consuming bar to approval as existing treatments exist, the progression free survival time must be longer, and fast-tracking would be harder to achieve, meaning a longer approval time than salivary gland cancer, and a longer time to further validate AVA6000 and the platform).

The bigger picture is that the success of AVA6000 trials will validate the platform.

Putting funding to one side, my main concern has been keeping ahead of the competition. Whilst AVA6000 should hopefully pass through approval relatively quickly and be profitable for a number of years for use with salivary cancer, soft tissue sarcoma, triple negative breast cancer, and potentially others, it seems likely that superior treatments will follow relatively quickly, including those under development by Avacta.

The development of AVA6103 and the potential to further enhance it (and other candidates) by combining it with anti-resistance compounds seems to bring Avacta to the forefront of cancer drug development with several advantages over ADCs, including, if I understand matters correctly, targeted ADCs such as those being developed by Oncomatryx (which has recently raised over £100m in funding including grants).

In my opinion, the advantages over ADCs were very well explained in the latest presentation although I did ask one question as this might be a further advantage. This was “Am I correct in thinking that ADCs are tumour specific, so even if successfully targeted to reduce side effects, they will only affect specific tumours, whereas a precision PDC will attack any FAP expressive tumours present in the body, including secondary tumours that might not even have been detected?”

So now I try, with my very limited knowledge, to put myself in the positions of Big Pharma and the Avacta board regarding potential deals...