Member Info for SisyphusShorter

Wyndrum, what is your opinion on the overall efficacy of Doxorubicin as a monotherapy for sensitive cancers?

As Dox has been used by oncologists for decades, it is fair to assume it is effective, no? And if there were indeed a way to make it tumour activated and less systemic, that would only improve its already-proven effectiveness, right?

So, why are you as yet unconvinced AVA6000 isn't efficacious? What data would persuade you otherwise? Even though we have some already very impressive data for it for Salivary Gland Cancer, which historically is only modestly sensitive to anthracyclines?

Touk, believing that AVA6000 is Ribena by extension also means believing that Doxorubicin is also Ribena, which is nonsensical given it is one of the most widely used chemotherapies in the world.

And again, this is a phase 1 study to prove SAFETY, not efficacy. The fact we are already seeing promising signals of efficacy in a phase 1 is very, very encouraging. Especially in highly pre-treated patients with chemo-resistant tumours, and in SGC which is historically intrinsically insensitive to the anthracycline class.

Because starting another phase III trial requires a huge amount of regulatory proceedings and planning, for one. The company must:

1. secure full FDA/EMA protocol approval,

2. update its IND dossier,

3. complete toxicology bridging,

4. negotiate CRO contracts,

5. align manufacturing under GMP for P140.

Immupharma’s recent updates confirm they’ve been finalising the revised trial design, patient‑stratification criteria, and regulatory feedback—steps that must be completed before recruitment can legally start.

The delay reflects compliance, not inaction, and ensures the restarted P140 Phase 3 proceeds on a stronger, regulator‑approved foundation. Plus, they've already announced they're in the process of preparing a manuscript on P140 to a peer-reviewed journal, which is a necessary step for third-party recognition of P140's effects on chaperone-mediated autophagy.

I'll do my best to answer WHY, Viking. In short, chemotherapy doesn't act instantly.

Topoisomerase-1 agents take anywhere from 6-12 weeks to start actually shrinking tumours. First patient dosed exactly 8 weeks ago as of yesterday, as per Avacta's previous RNS announcing this - so we're still pretty early into the trial. It'll then take at least 2 follow up CT scans, at least a month apart each (if not longer), before they can confidently say tumour size has decreased. Oh, and you'll need several patients. Because an n=1 simply won't cut it. And each patient will need to be dosed at intervals, probably a day minimum, in order for the trial to be safe. And remember, this is a PHASE 1 trial. It isn't phase 3. If that's what you're after, I suggest you find another stock.

This isn't an antibiotic or painkiller. It'll take months to work. So be patient.

In a small Phase 1, you don’t expect big response rates; you mainly look for disease control and durability - that's the point of phase 1, is it a "safe" drug, not "is it an effective drug".

Regardless, a 90% disease control rate with PFS not yet reached is a strong early signal in SGC, a disease with limited options. It suggests real anti‑tumour activity, not just a “well‑tolerated placebo.”

As follow‑up extends, we’ll get a proper median PFS and maybe duration‑of‑response data for those partial responders. And, if PFS clearly exceeds typical outcomes for heavily pre-treated SGC, then that strengthens the case for a dedicated Phase 2 and possibly an orphan‑type strategy.

Thanks thevid, what a great read. Really underlines the monumental potential of what Avacta's science team and leadership have on their hands. Shame I couldn't make science day and meet them in person.

Ah understood.

Thanks BV some good info there. However, with AVA6000/AVA6103 a Drug-Peptide Ratio "DPR" is probably more appropriate. Also, the fact that the cleavable peptides are much, much smaller than antibodies should decrease the probability of solubility problems, no?

I think, personally, that AVA7100 is a low priority for Avacta right now, given that AVA6103 is in its very early stages, and AVA6207 is probably sitting "in reserve" so to speak, in case they find uncharacteristically high levels of camptothecin drug resistance in the tumour types they're targeting in the phase 1 trial. Adding a DDRI or MMAE would, in theory, overcome this challenge. Then again, the whole point of the TEMPUS collab was to identify SHLFN11 genotypes conferring a higher degree of susceptibility to exatecan.

I would be surprised if Avacta had plans for a triple-warhead PDC (maybe a mini-chemo regimen, with 3 complementary agents to target a specific cancer), and if they did I wouldn't expect this until the FAP-cleavable system had been fully characterised. I'm not sure how long this will take. Could be weeks, or years. Exciting nevertheless!

GLA

Sorry Rookie, when you say "there is no way of diagnosing auto immune diseases at the minute", could you elaborate? Because....

Anti‑CCP (ACPA) — >95% specificity for rheumatoid arthritis, predicts erosive disease.

Anti‑Jo‑1 — Specific for antisynthetase syndrome and polymyositis, associated with interstitial lung disease.

Anti‑Mi‑2 — Highly specific for dermatomyositis, associated with classic skin findings.

Anti‑TPO — Strongly associated with Hashimoto thyroiditis and autoimmune hypothyroidism.

Anti‑GAD65 — Specific for type 1 diabetes and stiff‑person syndrome.

Anti‑AChR — Highly specific for myasthenia gravis; found in ~85% of generalized cases.

Anti‑Centromere — Very specific for limited cutaneous systemic sclerosis (CREST).

And finally, Anti-dsDNA and Anti-Smith antibodies for Lupus (SLE).

Sure, none of the above auto-antibodies are 100% diagnostic (nothing ever is - their presence needs correlating with clinical and biochemical findings), but to say we can't diagnose autoimmune diseases at the minute just isn't true.

Nice

So most cancer cells take around 36 hours to divide, and tumours can double in size over the 1-3 months, obviously this varies with different tumour types (for example anaplastic carcinomas divide more rapidly than some slower growing types). But short half lives DOES NOT mean short duration of action.

Most antineoplastics are cleared from plasma within minutes to hours, but their mechanism of action in most cases is to create lasting intracellular injury. For example, platinum agents form stable DNA crosslinks, antimetabolites like 5FU form complexes and cyclophosphamide metabolites irreversibly alkylate DNA. This DNA damage is still present when the cell divides a day and a half later, they don't need to be entirely cell-cycle-phase-specific (some are).

If we go back to anthracyclines like doxorubicin (AKA the warhead of AVA6000), these intercalate into DNA and persist in the cell nucleus (intracellular retention), so the effective half-life in the cell is much longer than the measured plasma half-life.

Hope this clears things up.

GLA

Hi Bella,

So a bunch of chemotherapies can be augmented with immune-stimulating compounds, whether they be T-cell receptor agonists or cytokine analogues (think Rituximab in the R-CHOP NHL regimen regimen, or Anktiva with non-resectable bladder cancer). But they are rarely, if at all, effective alone. They help modulate the immune response but they aren't cytotoxic in their own right. Synergistic use of an immunotherapy coupled with an Avacta PreCISION agent is probably a long way away.

GLA

Cancer incidence and prevalence has been steadily rising since the 1990s so obviously covid has nothing to do with it (and unlike Herpesviruses and HPV subtypes, Covid has so far not been demonstrated to be oncogenic). The west also has an ageing population so cancer will inevitably become more commonplace. We're also far better at screening and crucially, early diagnosis. Either way, the need for more effective drugs is increasing.

And for those doubting whether AVA6000 will maintain effectiveness post-cleavage in the TME, I suggest you read up on Anthracycline mechanisms of action and tumour resistance pathways.

Could this lack of movement be down to the trial already being priced in ever since the LOI getting signed last year coupled with Iliad securing their funding? Back in Feb/March hVIVO went from 6p to 9p on the iliad news, and that's broadly where we are now.

BUT it does show the degree to which people are interested in Avacta's technology and want to meet the team and hear what they have to say.....

Which in itself, is a very good sign.

GLA

Yes but what source/article is DEEPSEEK referencing in this instance?

I would be highly cautious of the temporality and accuracy of the sources that your AI is using in this instance, are you sure it is referencing up-to-date information?

Do we reckon that they'll initiate AVA6103 first and then also run AVA6000 phase 2 later in the year, and have both trials running together?

Yeah I'm pretty sure your chatbot is hallucinating, there has been no further news of EQT being involved whatsoever. Might wanna check your info before you ask AI to make stuff up....

Either this is old info from last month that you've only just come across, or you've just posted inside information regarding something new. Which is it.