Richard Armstrong

#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’.

#AVCT AVA6103 began end of March. On 16 September AVCT announced “clinical proof of mechanism for the preCISION platform.” We now know the reason the CEO was happy to state that: they already sat on biopsy data which confirmed the tumour reservoir model in human. The CEO went on to say (last week, interims) this is the most remarkable alignment of pre-clinical and clinical data she has seen in over two decades. So, we know: They sit on biopsies. They flew through C1,2,3,4. The safety profile is phenomenal. They are sustaining the release of Exatecan (for days) in human. They sit on confirmed platform technology. Given they have “a few” biopsies “in their back pocket”, these are likely coming from both mandatory backfill and not mandatory consent. Bingo is demonstration they have established a dose:response relationship as the cohorts have escalated and this translates into signs of effigy (which then increase as the dose escalates). Do they already have that? Well, they had a stage 4 pancreatic cancer patient still on drug in September (March dosing), they went after pancreatic again in C2, again in C3, then headed to AACR pancreatic. All of the C3 patients remained on drug at the beginning of September. The (modern, best practice) criteria to backfill in BOIN is efficacy. See MD Anderson’s public criteria. As ever, Coughlin only tells you she suspects she’s going to ace the test when she already knows the answers. All eyes now on how fast they move through Cohort 5. Cohort 5 is scheduled to be equivalent to the absolute dose of Enhertu so the speed of it will be the perfect test of preCISION’s specificity. Jet plane.

#AVCT have biopsies from AVA6103. Therefore, they knew they had replicated the tumour reservoir pre-clinical model at the time of the proof of mechanism RNS. Unsurprising, but wonderful to hear confirmed. As ever, all the peacocking was only done in the knowledge it already works. AVA6103 now running at 5 weeks per cohort. Astounding.

Well, there’s one of my investor meet questions answered in advance. Surprised this tweet is not getting more traction. It tells you the 6103 human data is matching the animal data with “remarkable alignment” #AVCT’s AVA6103 so clearly knocking it out the park.