AM23

#AVCT Cohort 1 Began end of March On 10 September, two patients remained on drug. That’s 5.5 months of disease stabilisation across stage 4 pancreatic cancer patients. Achieved with a 1.5mg dose of AVA6103. I.e. their tumours are not seeing progression. Cohort 2 Began ~mid May On 10 September, five patients remained on drug. That’s ~4 months of disease stabilisation across stage 4 pancreatic/CRC/cervical cancer patients. Achieved with a 3mg dose of AVA6103. I.e. their tumours are not seeing progression Cohort 3 Began ~early July On 10 September, (all) seven patients remained on drug. That’s ~2.5 months of disease stabilisation across stage 4 pancreatic/CRC/breast patients. Achieved with a 4.5mg dose of AVA6103 I.e. their tumours are not seeing progression Cohort 4 Began began ~mid August Dosing 6.8mg. Just below the Enhertu equivalent. Cohort 4 has completed enrolment as of 23 October. Enrollment is ongoing in both arms of the study. 8 months into trial end of November. It is quite clear AVA6103 is working. In human. Funded well into May 2027. That’s ~7 months of funding after a 68p fundraise which saw the directors take £660k. Cohort 5 (current cohort) projected to match the absolute dose of Enhertu. Q2W scanned every 8 weeks. Q3W scanned every 6 weeks. Couple of biopsies up their sleeves. They know exactly what this drug is doing 7.5 months into trial. The amount of ‘ hot takes’ I’ve read which are concerned about “funding into May when AVA6103 efficacy is not due to H1 2027” demonstrates enormous naivety. For two reasons: (1) the trial is flying, you’ll see efficacy early H1 2027 at this rate; (2) the efficacy data (as a package) for AVA6103 is actually irrelevant for the assets AVCT is seeking to deal on: a 3rd party warhead; AVA6000; AVA6207. Yes, the AVA6103 data supports the negotiations but they are not dealing on AVA6103. Proving AVA6103 is working (to the extent the tech can transfer to a third party warhead) was done when they RNS’ed preCISION was proven. Partners will receive this data under NDA on a constant basis. Far more important are the commercials of those deals, which improve as the AVA6103 data grows. That is to say the 6103 data *supports* the value discussion, rather than being the arbiter of any deal(s). Crazy thought I know, but they have a strategy. X3 separate deal avenues to deal on before May 2027. Lots of noise. Little logic.

#AVCT Novartis bought FAP2286 from Clovis in bankruptcy. $50m upfront; $333.75m in regulatory milestones (split equally between P1b; P2; P3); $297m in future sales payments. FAP2286 had dosed 11 patients at the time of sale. Efficacy: 1 patient of the 11 treated in Phase 1 saw a partial response. Safety: 45.5% of patients saw Grade 3/4 adverse events. You'll struggle to find a better representation of how cheap AVCT (£311m) is today than this sale. Achieved in bankruptcy. X2 drugs in clinic, north of 150 patients dosed across those programmes. A clear USP. Going after ADCs. Safety impeccable. No loss of activation enzyme on tumour destruction. AVCT could down all tools tomorrow, put the entire Co up for auction and sell for multiples of today’s SP. Funny old market. I’m a buyer here. AVA6103 is currently reading out critical C3 data (and every oncologist linked to the trial is promoting their collaboration…).

#AVCT AVA6000 contains a peptide. That peptide masks doxorubicin to the extent an 80 year old suffering from triple negative breast cancer is able to safely receive preCISION-doxorubicin. And work. The risks of chemotherapy induced toxicity due to reduced organ reserve, comorbidities and general frailty for an 80 year old are clear. Yet it’s working. Quite clearly. Why is it working? It has an exceptional safety profile. Due to this peptide’s exceptional specificity. Now consider the same peptide is in AVA6103. AVA6103 has an additional modified capping group and a linker (which are designed to sustain the release of Exatecan for days, rather than hours). We know from the human PK to date, that is exactly what AVA6103 is doing (with exceptional alignment between pre-clinical and clinical data). It’s extending release of Exatecan because the capping group and linker are working. In human. It’s safe because the peptide (employed in both AVA6000 and AVA6103) is so specific. We have seen the clean safety profile through cohorts 1-3 of AVA6103. Thanks to the peptide. We have seen the FDA remove the dosing limit (for the first time in the history of a P1 drug) in AVA6000. Thanks to the peptide. We are now seeing just how safe this peptide makes toxic drugs. 5 & 1/4 years of combined data back this up across Top1 and Top2 inhibitors. Tomorrow AVA6103 will be 30 weeks into clinic. Tomorrow AVCT will outline how AVA6000 is demolishing the benchmark in Salivary Gland Cancer. A prolonged median PFS of 11.4 months. That is nearly doubling the benchmark in the first and second line setting (both chemotherapy and targeted therapy). AVA6000 in SGC deals on this PFS. Quite clearly. In addition to all this, I can’t help but wonder whether AVA6000 in TNBC is going to also find a partnership with generic Keytruda in the future. Patent expiry in 2028? $30+Bn pa drug. Often used in tandem with doxorubicin which has now been made safe by preCISION. Keynote 522(P)? The trial Coughlin said she would most like to run for 6000. AVA6207 on the cusp of revealing its warheads. AVA6103 biopsies incoming. AVA6000 demolishing the PFS in SGC. Looking forward to hearing more about FAP recruitment, durability and the real world impact of AVA6000 when the company explains the findings to the market tomorrow. ‘Bloody science project’.

Most important sentence in an #AVCT RNS for a long while. We’re home. Nearly dry. 🚀

#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…