TVR5 fully supports the #AVCT board’s strategy to protect the inherent value of the pipeline, given the strength of the AVA6103 data to date. We expect the board to close its first validating deal in Q4 2026, following this bolstering of the company’s negotiating position.

You don't just add 7 new trial sites at some of the most prestigious oncology centers globally unless your trial is going well. Huge cost for this but even bigger validation = Green lights. Gastric in focus and recalling CC comments from a previous event a year ago where she stated Gastric was her first indication pick at the time to see responses! Very telling they have been telling us a lot about the progress with PDAC the likely hardest of the 6 indications to treat first....Have they cracked them all? Well done AVCT #AVCT mskcc.org/cancer-care/clinic…

#AVCT Enhertu Phase 1a was very good at disease control, even at the lowest doses. 21/23 saw stable disease. There were 10/23 partial responses. All of these partial responses, bar x1 patient, came at a dose of 5.4mg and above. The single responder below this dose threshold was at 3.2mg. There was 1/23 complete response. There were just 2 cases of disease progressing. x1 at 3.2mg and the other dose not disclosed. If AVA6103 is not controlling disease at the 6 month marker, it is not going head-to-head with Enhertu. Yet there is not a single mention of “stable disease” or “disease control” in either of the recent RNS (post proving of the platform). Instead, AVCT simply says it expects efficacy to follow, it expects a tumour reservoir, it expects the preclinical results to translate to clinic. There is little chance the company speculates on these expectations, without having seen AVA6103 enabling disease stabilisation at these low dosing levels to date. Because that is exactly the Enhertu benchmark they are directly comparing against. At the RP2D (5.4mg) the median time to response (TTR) for Enhertu is just 1.6 months. I.e. The middle point in time when half of the patients who eventually responded to Enhertu first showed a clear improvement (tumour shrinkage that qualified as a partial response) on their scans. I.e. it works very quickly at the big doses and is likely to show at the time of the first scan (6 week marker). DL4 should be right up there with Enhertu’s median TTR. If not better. The DL3 cumulative exposure is now punchy. 7/7 remain on drug as of the last update. To top it off AVCT is talking AVA6103 at a pancreatic cancer conference (an indication which Enhertu simply did not work, no matter how high the dose or the HER2 amplification). A good reminder just how hard pancreatic is to crack. So, what does matching or bettering Enhertu’s phase 1 data actually mean at this stage? Easier to look at what the clinicians were saying about Enhertu’s (complete) Phase 1 data set. Copied below. What followed for Daiichi? Fast Track was granted based on the reported 22 patients treated at the time (20 evaluable). Avacta is moving at twice the speed Daiichi was at this stage…

#AVCT #Avacta #AVA6103 #PancreaticCancer #Oncology

If you assume the three AVA6103 dose levels were split evenly over the last c.six months, #AVCT will have scanned the first cohort three times; the second cohort twice; the third cohort once by this juncture. The dose levels used were 1.5mg, 3mg, 4.5mg, respectively. These levels were chosen so that the absolute quantity of toxin administered is roughly the same as the absolute payload quantities patients received at the lower end of the Enhertu dose-escalation range. Remember Enhertu has a drug to antibody (DAR) ratio of 8:1 and DXd is not Exatecan, so it’s not a simple comparison. But Avacta is designing their trial around Enhertu’s P1a purposefully. They want to draw comparisons to those absolute ‘absolute levels’: “The first three dose levels are similar to the absolute payload dose levels in the published Enhertu® Phase 1 trial (Doi, et al. 2017)” That trial (DS8201-A-J101) was the first test of Enhertu. It took Daiichi just over a year to dose 24 patients. 23 of those 24 patients were evaluable. AVA6103 has dosed 19 patients in ~5.5 months. Tier 1 pharma would be impressed by this speed. Going at near double the speed of Daiichi Sankyo. Those P1a Enhertu patients had either advanced breast or gastric/gastro-oesophageal cancer. x3 patients each at 0.8, 1.6, 3.2, and 8.0 mg/kg; x6 patients each at 5.4 and 6.4 mg/kg. No dose-limiting toxicities occurred, and the maximum tolerated dose was never reached. If you look at these P1a results from Enhertu you will see efficacy which met objective response criteria (i.e. a complete response or partial response) was almost non-existent below the 5.4mg dose. Just one partial response occurred (at 3.2mg). However, you will also see the disease stabilisation which occurred at those lower dosing levels (<5.4mg) was very good with just 2/23 disease progressions amongst the very sick patient population, even at these lower doses. Now consider the indications AVA6103 is in and the stage those patients are at. Then consider in some of the indications AVA6103 is going after (eg pancreatic) Enhertu simply didn’t work, no matter how high the dose or how strong the HER2 IHC reading. NB: Enhertu did not dose pancreatic in P1a, it attempted it later (once it had confirmed activity in other indications). So, if your comparison is ‘what did Enhertu do’ (as Avacta’s is) they will want to be seeing consistent disease stabilisation amongst the lower dosing cohorts of AVA6103, in order to be sure the platform is working and you have a read across. Without disease stabilisation amongst the lower cohorts, you have no idea whether your PK is translating to efficacy, which is what matters. Enhertu saw 9 of its 10 P1a objective responses achieved at >5.4mg. These were all Partial Responses, no Complete Responses occurred. Now consider AVA6103 doesn’t plan on reaching the equivalent approved Enhertu payload equivalent until DL5. As they escalate AVCT expect to see a dose-response relationship. So what is “preCISION enabled Exatecan” aka AVA6103 actually doing before it gets to DL5 (given Enhertu did not start to see any partial responses (bar one at 3.2mg) until 5.4mg+)? Let’s not forget BOIN enables grater jumps if the safety is good (which it is) yet AVCT do not intend to jump to the Enhertu R2PD equivalent until DL5. Why aren’t they utilising this freedom, given how good the safety is? After all, that’s what BOIN is for. AVCT knows its masking via the peptide works. The initial safety findings have been consistent and superb. They want to know if the drug is efficacious (at this early stage). This is where “dose density” comes into play and, crucially, where the company sees the impact of preCISION’s mechanism of action on efficacy at lower dosing levels (vs Enhertu). This is where AVCT start to see the technology truly differentiate. Note DL3 has seen no drop outs and impeccable safety since it began dosing.

#AVCT is a multi-drug biotech, sat upon a proven platform, which is currently perfectly replicating PK across 19 patients via a warhead which has never previously been harnessed. Execution of clinical strategy has been flawless. This is why TVR5 is so relaxed: preCISION works.

Yesterday, #AVCT not only proved their platform, they confirmed zero drop outs at DL3 (50% over the MTD of Exatecan). This cohort comprises very sick, stage 4 patients, who previously received Enhertu. They found their way onto AVA6103 because Enhertu failed to work for them.

You can draw a thousand analogies as to what this data means but you will still struggle to capture its significance for #AVCT and preCISION. Before you even get to looking at the impeccable safety data consider AVA6103 is now in six indications. In two of those six, Enhertu simply does not work: small cell lung cancer and pancreatic cancer. Forget Exatecan (which requires dosing every day for 5 days) to still return a horrendous safety profile. Small cell lung cancer is not typically driven by the enzyme HER2 so Enhertu cannot activate. Pancreatic cancer is just brutally stubborn (a force field of scaffolding-like structure sits around it) so even where the HER2 levels are very high (IHC 3+) it still does not work. AVA6103 by contrast is through dose level 3 with 0 drop outs and seeing 0% Neutropenia; 5% Thrombocytopenia; 5% Nausea; 16% Anemia, despite being 50% higher than the maximum tolerated dose of Exatecan. It’s a colossal start to P1a. They are now planning on taking ALL 6(!) indications into P1b. Again, consider Enhertu does not work in 2 of those 6. They’re obviously now targeting an expedited route with the FDA. For long suffering shareholders the question is no longer does it work but how does Avacta retain as much of its pipeline, for as long as it possibly can, until the inevitable takeover. Which now looks nailed on for 2027. As for Chris Coughlin… recall this clip before the AVA6103 trial began to appreciate her ambition. The constant throughout her steerage of Avacta has been she is always fifteen steps ahead. So what’s next? Finally, a huge thanks to Richard Hughes, without whom Avacta’s shareholders would resemble watermelon in a Nutribullet.

“The comparison of the preclinical modeled pharmacokinetic (PK) data and clinical trial PK data demonstrates an exceptional alignment through the first 3 dose levels with controlled release of exatecan” All we need to know. Phenomenal. #AVCT

Enhertu revenue projections..... 2026 - $5.4bn 2030 forecast $11.bn - $13.9 AVA6103 just smashed it on safety and dosing! AVA6103 has multiple times the scope of Enhertu which is HER2 limited. Avacta has a £375m mkt cap pre the open!!! Do you want a £10+ note for 80p? #AVCT

It’s very difficult to comprehend the magnitude of what #AVCT is seeking to achieve unless you’ve experienced the brutality of cancer 1st, 2nd, 3rd hand. Which unfortunately many have given the statistics. But it’s still hard to turn your head to the reality of ‘safety’ unless you’ve seen the effect if it. I definitely didn’t appreciate its significance on a practical level until recently. I assumed biopsies ‘just happened’. Consider only being able to take Enhertu if your cancer exhibits enough HER2 to activate. Consider not being able to have the biopsy (which tests whether your cancer is HER2 positive) because thrombocytopenia means your risk of bleeding out during biopsy is that high. If you can get onto the drug, consider the almost inevitable dose reductions and dosing breaks required due to the damage the drug will do to your body and frail state you are already in. Then consider <1% of the warhead in that ADC is hitting the tumour. Then imagine you don’t need HER2 because ~90% of cancers exhibit FAP. Then imagine the impeccable safety profile means very sick patients can safely accept the new drug. A few years who when ‘click chemistry’ company Shasqi had a link to the Nobel Prize in Chemistry I recall many suggesting Bachovchin could be in line for one of those. Then consider that technology, without the modifications made by Coughlin and Wilson, would not get close to addressing ~90% of solid tumours because of its limitations around what it could be attached to (e.g. dox). A high performance engine without a tuner. What will follow in Q3 (<11 sessions) is confirmation whether the unharnessed Exatecan can be harnessed. It’s very hard to quantify the implications of this, should it come, both on a human and financial level. Reminded Keytruda once exchanged hands for $1,000 on a term sheet. The ‘all knowing’ big pharma industry in a nutshell. Dumb luck. Nothing more.

#AVCT continue to present a pipeline which is only possible if those individual candidates sit upon a working platform. Yet another extremely bullish signal from the company.

RT @RAH00084: #AVCT The “reservoir effect”. Expect to hear a lot more about it. However, I struggle with the analogy. What does a big ar…

AVA6103 will confirm whether human data is replicating pre-clinical data in Sept. Proving the controlled the release of EXd sets #AVCT apart from every biotech which has historically failed to harness the warhead. On that event preCISION’s utility grows exponentially overnight.

Zeus #AVCT note: Base case (no human data/deal) - 109p AVA6103 working in human - 150p AVA6103 working in human & platform validating deal - 193p

Begging the obvious question, is #AVCT seeing activity in Stage 4 pancreatic cancer? If it is, via the extended release of Exatecan, shareholders can revisit their calculations as to what is possible for preCISION and this biotech. September 25-28.