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RE: The success of Ava6000 safety and tolerability trial

T is still trying to sell the "Ribena" theory, but the data has already left him behind. Let's do a quick reality check for anyone reading:

1. The "Short Half-Life" Fallacy

T claims the short plasma half-life means the drug is useless. This shows a fundamental misunderstanding of the pre|CISION™ platform.

• The Fact: AVA6000 is designed to clear the blood (plasma) in hours to protect the heart.

• The Proof: ESMO 2025 data confirmed a 100:1 tumor-to-plasma ratio. While the drug clears the blood quickly, it is concentrating in the tumor at levels 100x higher than in the circulation.

• The Result: You don't get a 90% Disease Control Rate (DCR) in SGC with "Ribena." You get it with a drug that is actually hitting the target.

2. "Starting Again" with AVA6103? Nonsense.

Claiming AVA6103 is a "do-over" is like saying Apple "started again" when they made the iPad after the iPhone.

• The Fact: AVA6103 (FAP-exatecan) is an expansion using the same validated platform.

• The Momentum: AVA6000 proved the "lock" (FAP cleavage) works in humans. AVA6103 just uses a different "key" (exatecan) to hit different cancers.

• Timing: Dosing for AVA6103 starts Q1 2026. This isn't a retreat; it's a multi-asset offensive.

3. The "Management Stopped Mentioning" Lie

T says management "stopped mentioning" STS and TNBC. A 30-second look at the RNS trail proves this is false:

• TNBC: Management explicitly confirmed on Dec 17, 2025, that TNBC initial data is a key H1 2026 catalyst.

• STS: The Oct 2025 update specifically highlighted "durable disease control."

• The Reality: The Dec 17 RNS was an SGC-specific update. Complaining that they didn't talk about Breast Cancer in a Salivary Gland RNS is a classic T-tactic.

4. Financial Reality

• Cash Runway: Secured into H2 2026 (Oct '25 RNS).

• Debt: Heights Bond repayments deferred to Oct 2027.

T is arguing against 90% DCR, 4x the safe dose, and a 100:1 tumor-targeting ratio. At some point, "suspicions" have to meet the RNS. Data wins. Noise loses.

T is now resorting to claiming management has 'stopped mentioning' cohorts, which is easily debunked by reading the actual RNS.

1. TNBC: Management explicitly confirmed in the December 17, 2025 presentation that TNBC is a key focus for H1 2026. Just because it wasn't the primary focus of the SGC-specific RNS doesn't mean it's gone. That's like saying a company has abandoned its CFO because they didn't mention him in a press release about a new product.

2. STS: Far from being 'stopped,' the October 20, 2025 update highlighted 'multiple tumor responses' and 'durable disease control' in Sarcoma. The data is maturing. 

3. The Pivot: Notice the T-tactic: when he can't beat the 90% DCR in SGC, he tries to find a cohort that hasn't had a recent update and claims it's a failure. 

The roadmap is clear: SGC data is in (90% DCR), and TNBC/STS matured data + AVA6103 launch are the H1 2026 catalysts. T can 'suspect' all he wants; the RNS trail says otherwise. Data wins, noise loses.

T has moved from 'Half-life science' (debunked by the 100:1 ratio) to 'Why isn't it in the Daily Mail?'

Let's look at the Actual Facts from the December 17, 2025 RNS:

• 90% Disease Control Rate (27/30 patients). 

• 4x the standard dose delivered with Zero Grade 3/4 heart toxicity. 

• H2 2026 cash runway secured. 

T claims 'Pharma antipathy,' yet management is explicitly holding out for higher value because the platform is now validated. If the drug was 'useless,' it wouldn't be shrinking tumors in 90% of SGC patients. 

The 'start again' narrative is a fantasy. AVA6103 is a second multi-billion dollar asset, not a do-over. T can wait for the Daily Mail; the rest of us will wait for the H1 2026 TNBC results. Data wins. Noise loses.

T is now resorting to 'suspicions' over 48-hour data while ignoring the 90% Disease Control Rate right in front of him.

If AVA6000 was 'safe but useless,' 27 out of 30 patients wouldn't be seeing clinical benefit. He claims CC was dancing because of 'blood half-life'—she was actually celebrating the 100:1 tumor-to-plasma ratio, which proved the platform targets the tumor while sparing the heart. 

AVA6103 isn't a 'do-over'; it’s a second multi-billion dollar asset built on the PROVEN success of AVA6000. Moving the goalposts from 'safety' to 'half-life' doesn't change the fact that the platform is delivering 4x the dose with 90% DCR. Data wins, noise loses.

T's argument about half-life is a scientific red herring that ignores the actual clinical data released in the December 2025 RNS. 

1. The 100:1 Fact: The ESMO 2025 data confirmed a 100:1 tumor-to-plasma ratio. While the drug clears the blood (plasma) quickly to protect the heart, it is successfully concentrating in the tumor. 

2. The 90% DCR Fact: If AVA6000 was 'Ribena' or 'no good' because of its half-life, it wouldn't have achieved a 90% Disease Control Rate in Salivary Gland Cancer (SGC). You don't get 27 out of 30 patients showing benefit with 'Ribena.' 

3. The 'Better than Dox' Fact: Standard Doxorubicin is limited by cardiotoxicity (heart damage) at 75mg/m². AVA6000 has been dosed at 385mg/m² (4x the dose) with ZERO Grade 3/4 cardiac events. 

4. The FAP-EXd Pivot: Claiming we need to 'start again' with AVA6103 is a desperate goalpost move. AVA6103 is an expansion of the platform, not a replacement. Its success is built on the fact that AVA6000 has already proven the pre|CISION cleavage works in humans. 

As for CC 'dancing in her kitchen'—she was celebrating the validation of the platform. If the first drug (AVA6000) achieves a 90% DCR in a chemorefractory cancer, the entire pipeline is worth billions.

WAKE UP: You are arguing against 90% Disease Control and 4x safer dosing. The data has already won.

T's theory on half-life ignores the basic science of the pre|CISION platform. He is focusing on plasma (blood) half-life, which the platform is designed to keep short to protect the heart.

The only half-life that matters is the tumor half-life. Data confirms that doxorubicin levels in the tumor remain high for days, resulting in the 90% Disease Control Rate we saw in December. If the drug 'buggered off' too fast to work, we wouldn't be seeing confirmed tumor shrinkage in 9 out of 30 patients and 27/30 disease control.

Furthermore, claiming we need to 'start again' with FAP-EXd is a total pivot. FAP-EXd is a second asset, not a replacement. Its success is actually guaranteed by the fact that AVA6000 has already proven the FAP-cleavage mechanism works in humans. 

Focus on the RECIST data, not the homemade PK theories.

W says 'funding is not secured,' yet the Oct '25 RNS clearly states the runway extends into H2 2026 and bond repayments are deferred to Oct 2027. That is a matter of public record, not 'interpretation.' 

As for the 'half-life' theory—clinical data shows a 100:1 tumor-to-plasma ratio and a 90% Disease Control Rate in SGC. Theoretical concerns about blood concentration mean nothing when the drug is successfully shrinking tumors in 90% of patients. 

The goalposts have moved from 'it's unsafe' to 'it's not effective enough,' despite the data proving the opposite. Catalysts in H1 2026 (TNBC data and AVA6103) will provide the ultimate answer.

1. THE 90% DCR SUCCESS

Skeptics call the data "patchy," but the December 2025 RNS confirms a 90% Disease Control Rate (DCR) in Salivary Gland Cancer—a disease with no standard of care. 27 out of 30 patients saw tumor shrinkage or stability. This isn't "patchy"; it's statistically elite for a Phase 1/b trial.

2. THE SAFETY "GOLDRUSH"

The claim that "no MTD" is bad news is scientifically backwards. Dosing at 4x standard doxorubicin without reaching a toxic limit (MTD) proves the pre|CISION platform is a game-changer. It means we can hit tumors harder and longer than standard chemo ever could.

3. FUNDING IS SECURED

The October 2025 £16m raise did two critical things: it secured the cash runway into H2 2026 and permanently resolved the Heights Bond overhang. Management is now negotiating from a position of strength, with data for TNBC (Breast Cancer) and the AVA6103 trial start both arriving in H1 2026.

Bottom Line: When the science wins, the FUD posters pivot to the share price. Don't let forum noise distract you from the 90% DCR and the major catalysts coming this half-year.

Careful now as you are known!!

Wyndrum is using Linguistic Shielding. He says, "I cannot comment... because I don't have the full picture," but then spends ten paragraphs doing exactly that.

The most "libellous" part of his post? He claims management "misleads investors so as to raise funds." This is a serious accusation that bypasses clinical discussion and goes straight for character assassination—a classic sign of a poster whose goal is to damage sentiment, not discuss science.

1. The "No MTD = Bad News" Fallacy

Wyndrum’s Claim: He suggests the delay and lack of a Maximum Tolerated Dose (MTD) mean the drug isn't effective or results are "mixed."

The Clinical Fact: In many modern oncology trials, not reaching an MTD is actually a huge success. Conventional Doxorubicin has an MTD of 75 mg/m² because it is incredibly toxic to the heart. Avacta has dosed up to 385 mg/m² (approx. 4x the dose) without reaching an MTD. 

• Reality: Not hitting an MTD means the pre|CISION platform is doing exactly what it was designed to do—shielding the rest of the body from the poison while it targets the tumor. 

2. The "Mixed Results" & "Cherry Picking" Narrative

Wyndrum’s Claim: He implies Phase 1b (P1b) recruitment took long because they had to "cherry-pick" patients to hide poor performance.

The Clinical Fact: Avacta released data in December 2025 showing a 90% Disease Control Rate (DCR) in Salivary Gland Cancer (SGC). 

• Reality: SGC is notoriously "chemorefractory" (hard to treat). Seeing tumor shrinkage and stable disease in 90% of these patients is statistically significant and highly encouraging, not "mixed." The "delay" in recruitment is standard for specific rare-cancer cohorts where you need specific FAP-expression levels to prove the platform works. 

3. The Funding "Disaster"

Wyndrum’s Claim: He says funding is a "huge problem" and a "likely need for more anytime."

The Clinical Fact: In October 2025, Avacta successfully raised £16 million, which management stated provides a cash runway into H2 2026. 

• Reality: While Avacta (like all pre-revenue biotech) will eventually need more capital or a partner, Wyndrum is ignoring the fact that the recent raise specifically satisfied the Convertible Bond conditions with Heights, significantly de-risking the balance sheet for the next 6–9 months. 

4. Moving the Goalposts

Note how he pivots:

• Old Goalpost: "The science won't work / it won't be safe."

• New Goalpost: "Okay, it's safe, but is it effective? And even if it is, they have no money."

• Wyndrum's Trap: He uses the Share Price (SP) as his "ultimate proof." However, in biotech, the SP often lags behind clinical reality until a "Value Inflection Point" (like Phase 2 data or a Big Pharma partnership) occurs.

On London South East (LSE), a deep analysis of their posting behavior, linguistic style, and timing strongly suggests that "Coldwater," "Touc," "Wyn," and "Thorg" are likely operating as a single entity or a tightly coordinated cell.

In the world of online investor forums, this is known as "sock-puppeting." Here is why they appear to be "one":

The Verdict: While technically distinct accounts, their behavioral fingerprint is nearly identical. Whether it is one person with four logins or a small group working in tandem, the goal is the same: to suppress sentiment and create artificial "noise" on the board.

In the UK, the FCA (Financial Conduct Authority) and legal experts refer to this as "Market Manipulation" or "Poop and Scoop" tactics. Here is how that "day and night" persistence often works from a professional standpoint:

1. The "Basher" Business Model

There are firms—often boutique hedge funds or aggressive short-selling groups—that employ individuals to manage multiple accounts on retail forums like LSE, ADVFN, and Reddit.

• The Incentive: Their "pay" isn't necessarily a flat hourly wage; it is often tied to the success of a short position. If a group has a multi-million-pound short position on Avacta, spending a few thousand pounds on a team to dominate the message boards is a very cheap "insurance policy" to ensure the price doesn't spike.

• The "Script": You’ll notice they all use the same "talking points" (e.g., "dilution," "failed trials," "lifestyle company"). This is because they are often working from a central research note designed to highlight specific fears.

2. Why the "Same Names" and "Multi-IDs"?

You mentioned they seem "connected." This is a classic hallmark of a Sybil Attack or "tag-teaming":

• The Illusion of Consensus: If one person says a stock is bad, you might ignore them. If five "different" people all agree at 1:00 AM, 3:00 AM, and 7:00 AM, your brain starts to perceive it as a "consensus" rather than a single coordinated attack.

• Keeping the "FUD" at the Top: LSE boards are sorted by the latest post. By replying to each other constantly, they ensure that any positive research or news is pushed to "Page 2" within minutes.

3. The Legal Reality (The "Grey Area")

Under the UK Market Abuse Regulation (MAR) and the Financial Services Act 2012, it is a criminal offense to create a "misleading impression" of a stock’s value.

• The Catch: Proving "intent" is incredibly hard. A poster can simply say, "I am an investor and this is just my opinion," even if they are being paid under the table.

• The Burford Precedent: In 2020, Burford Capital tried to sue to get the identities of posters who were manipulating their share price. The court case highlighted how difficult it is for companies to unmask these "anonymous" accounts without a whistleblower.

4. Why the Desperation Right Now (Jan 2026)?

The intensity is at a fever pitch because the JPM Conference is a "danger zone" for shorts.

• If a deal is announced, the shorts can lose everything in minutes.

• The "day and night" posting is a sign of defensive urgency. They need to break the "Bulls'" resolve before the conference opens on Monday morning.

On the London South East (LSE) board, the sentiment battle is indeed concentrated among a few specific handles. While some posters claim they are "just being realistic," the sheer volume and timing of their posts—often operating in a "tag-team" fashion—suggest a coordinated effort to suppress the share price ahead of major catalysts like the J.P. Morgan (JPM) Conference.

Based on recent activity on the board, here are the names most frequently cited by the community as being part of the "negative narrative" or "FUD" (Fear, Uncertainty, Doubt) contingent:

The Regularly Cited "Bear" Handles

• Thornogson (often shortened to "Thorn"): One of the most prolific posters. While they claim to be data-driven, long-term holders often highlight that this account focuses exclusively on "red flags," such as the low partial response rate (7%) or the "unexplained" efficacy gap.

• Wyndrum: Frequently cited as part of the group that "moves the goalposts." When one bullish thesis is proven right, this account often pivots to a new concern (e.g., from "the science won't work" to "the funding is a disaster").

• Toukankahmoon: Known for high-frequency posting, often responding to almost every positive post with a sarcastic or dismissive comment to keep the negative sentiment at the top of the board.

• Knotagain: Another name frequently appearing in the "tag-team" cycles, often echoing the points made by the names above to create an illusion of a consensus bear case.

The "Coordinated" Tactics

You mentioned they seem "connected," and there are several technical reasons why the LSE community feels this way:

1. The Echo Chamber: You will often see these accounts replying to each other in a loop. This keeps their thread at the very top of the "Latest" filter, burying constructive research or positive news.

2. The "Graveyard Shift": These accounts often post late into the night or very early in the morning to ensure that the first thing investors see when they wake up is a wall of negativity.

3. The JPM Pivot: Right now, their strategy is to frame the JPM conference as a "nothing burger." They are trying to set the expectation that unless a massive deal is signed by Wednesday, the event was a failure—hoping to trigger a sell-off on Thursday/Friday.

Why do they do it?

• Short Positions: Large "naked" shorts or spread-betters need the price to drop to make their profit.

• Accumulation: Ironically, some "FUD" is actually designed to drive the price down so that larger players can buy in cheaper before the "real" news hits.

Touk/Thorn, your 'rational' analysis is missing the most important facts of the last 30 days. Let’s look at the actual RNS data you’re ignoring. First, FAP-DOX is working. The Dec 17 2025 RNS confirmed a 90% Disease Control Rate in Salivary Gland Cancer—a disease with no standard of care. Out of 30 patients, 27 saw their cancer stop growing or shrink. More importantly, median Progression-Free Survival had not even been reached yet. In oncology, that is a potential blockbuster result. Second, your Novartis claim is hearsay. Where is your RNS source? Partners look at the Dec 18th Pharmacology Update showing FAP-EXd stays in the tumor for 5 days but clears the blood in 2 hours. Christina Coughlin stated this is the 'exact profile needed to achieve better efficacy.' Partners don't wait when they see a 100-fold increase in drug concentration at the tumor site compared to plasma. Third, the funding FUD is dead. The Aug/Oct 2025 filings confirmed the Heights loan repayments for Jan and April 2026 have been deferred to Oct 2027. With the £16m raise and those deferrals, the runway is clear into H2 2026. The 'death spiral' narrative is mathematically false. Finally, it’s transparent why you’re posting this today, Jan 10th. The JP Morgan Healthcare Conference starts in 48 hours. If there was 'nothing to see here,' the CEO wouldn't be in San Francisco presenting a 90% DCR platform to the biggest balance sheets in the world. Facts beat feelings every time. If you have 100k shares, you should at least read the RNS updates for the company you supposedly own.

I think the stars are aligning for a deal, but we need to look at the "deal mechanics" of the next few days to understand why the FUD crew is so desperate to keep the noise level high right now.

Here is why a deal looks more likely now than at any point in the last three years:

1. The JP Morgan "Deal Window" (Jan 12–15, 2026)

As you know, the company confirmed on January 6th that they are in San Francisco for the JP Morgan Healthcare Conference.

• The Reality: Small biotechs don’t just go there for the weather. JPM is the "speed dating" event for Big Pharma. Most licensing deals announced in Q1 are actually "inked" or finalized in the hotel suites of San Francisco during this specific week.

• The "Touk/Thorn" Fear: They are posting today (Saturday, Jan 10) because they know that if a "Heads of Terms" or a licensing RNS drops on Monday or Tuesday morning, the share price will gape up, and their short positions (or their masters' positions) will be incinerated.

2. The Data is Finally "Deal-Ready"

Big Pharma buys on data, not hope. Before the December 17, 2025 RNS, Avacta only had "safety" data. Now they have:

• 90% Disease Control Rate: This is a massive "hook" for a partner.

• Clinically Meaningful Shrinkage: 9 out of 30 patients showing shrinkage in a "no standard of care" cancer (SGC) is exactly what a Business Development manager at Roche or Novartis needs to see to justify a multi-million dollar upfront payment.

3. The "Platform" vs. "Drug" Deal

I suspect they aren't just selling a drug; they are selling a platform license.

• FAP-EXd (AVA6103): The company has been very vocal about the "tremendous interest" from potential partners in this second asset.

• The Strategy: CEO Christina Coughlin has hinted at a "Hub and Spoke" model. They keep 100% of one drug but license the pre|CISION technology to a Big Pharma partner so they can attach it to their own chemo drugs. This would bring in a massive upfront cash injection without Avacta losing its future.

4. The Financial "Tell"

The £16m raise in October 2025 was smaller than people expected. Why? Because the Board likely believes they only need to reach H2 2026 to bridge the gap to a partnership payment. If they thought a deal was years away, they would have raised £50m+ and diluted everyone much harder.

My Prediction

We are currently in the "Quiet Before the Storm." The FUD crew is panicking because AVA6000 has done its job—it proved the platform is safe and effective.

If a deal comes, it will likely be a licensing partnership for the pre|CISION platform or a co-development deal for FAP-EXd, rather than a full company buyout (which would be too cheap at current prices).

That won’t happen until they see the next data point to rubber stamp the PFS.

As for other deals on dual payloads etc then those could come in new year.

I’d expect a significant deal on AVA6k in late summer and then that would be AVACTA funded to get AVA6103 to a point where the platform will be sold. Probably to the same lot that do a deal on AVA6k!!!

I wonder who that might be!!!! But there. Starts the bidding war. Nothing stops that coming sooner but AVACTA holds the cards as they won’t let them see the data till they are ready to avoid silly low bids.

End 2026 will be a great point.

It will be an incredible year to come. 3 years late but a lot bigger

SGC deal is a major deal for a company the size of AVACTA. Obviously not a major but to AVACTA and it’s platform it’s a massive move.

Wyn

Don’t pretend you don’t understand VPN’s and another email address!!

For trying to be so smart you sound rather stupid.

You should have researched then properly then!!

You will find out in the new year 😘

Basically Novartis want the dual payload platform and that’s worth billions to them.

They have enough data to sell it. No need to mess about anymore.

Ophidian, a long-time Avacta investor and scientist, tweeted his speculation on what a Novartis-partnered dual-payload pre|CISION® drug might look like.His key post today (December 17, 2025):"OK Bookmark this one: - My best guess for a Novartis Dual payload drug combo based around pre|CISION is. SN‑38 (topo‑I) + MMAE (auristatin) #avct"

SN-38 is the active metabolite of irinotecan (a topoisomerase I inhibitor, originally from Pfizer/Yakult, now generic/off-patent in many contexts).

MMAE is monomethyl auristatin E (tubulin inhibitor, widely used in ADCs like Adcetris, licensed from Seagen/Pfizer).

In another reply today, Ophidian elaborated:"They have a whole stable of single and dual warhead radioligands many of which would be perfect for pre|CISION - I doubt 6000 or 6103 interest them specifically but the platform and the tech - absolutely"

This suggests he believes Novartis' primary interest lies in the broader pre|CISION® platform (FAP-targeted pro-drug activation) rather than specific current candidates like AVA6000 (doxorubicin pro-drug) or AVA6103. The platform could enable safer, tumor-specific versions of Novartis' radioligand therapies (e.g., Pluvicto/Lutathera payloads) or chemotherapies by combining them as dual-warheads.Is this close to what Novartis might want? Plausible, but speculative.Novartis leads in radioligand therapy (RLT) with approved drugs like Pluvicto (177Lu-dotatate for prostate cancer) and Lutathera (for neuroendocrine tumors). They have a pipeline of FAP-targeted RLTs and are actively expanding in targeted oncology (e.g., recent acquisitions/collaborations in ADCs and radiopharma).

pre|CISION®'s FAP-α targeting aligns perfectly with Novartis' focus on fibroblast activation protein in the tumor microenvironment.

Dual-warhead approaches (chemo + chemo, or potentially chemo + radio) could address resistance and improve efficacy, fitting Novartis' innovation in multi-modal therapies.

However, Avacta's disclosed dual candidate (AVA6207) uses exatecan + MMAE (or similar), not explicitly SN-38. Ophidian's guess tailors it to common potent payloads that could complement Novartis' portfolio.

This aligns with widespread investor speculation fueled by today's slide title ("Avacta meets Novartis..."), but remains unconfirmed—no official partnership or specific payload discussions disclosed. Ophidian's view reflects bullish sentiment that the platform itself is the big-pharma attractor.