Sometimes it is important for investors to take a breath, step back from the market’s day-to-day ramifications and instead focus on the big picture.
Back in August 2021, Avacta (AVCT) dosed its first patient with AVA6000 (a tumour targeting prodrug being developed to treat soft tissue sarcomas) at the UK's Royal Marsden hospital. The primary goal was to test the drug’s safety tolerability and wider FAP-activated preCISION platform in reducing systemic toxicity of doxorubicin in humans.
Two years and four months on, the results so far from this multi-centre international Phase 1a clinical trial have been truly phenomenal.
Today the company said that AVA6000 had shown outstanding safety characteristics across all 7 cohorts – the last one being conducted at a concentration level 3.5x greater than standard doxorubicin. Indeed, so good is the prodrug at shielding healthy tissues from adverse side-effects that no upper bounds to its usage (ie Maximum Tolerated Dose) have yet been found. Which is frankly remarkable.
Importantly too, this potentially opens the door to dosing patients more frequently, as well as at higher levels or for longer cycles than has ever been allowed before.
But that’s not all.
Way beyond even the trial's original design, both AVA6000 and the preCISION platform have also demonstrated "encouraging preliminary clinical signs of anti-tumour activity", validating the mechanism of cleaving the cytotoxic solely within high FAP tumour microenvironments - and crucially not elsewhere in the body (eg triggered by other human enzymes).
Indeed, a 59-year-old male with Undifferentiated Pleomorphic Sarcoma has already experienced a significant 65% reduction in tumour volume with a duration of response >6 months and ongoing. Elsewhere, a number of other patients with different cancers have seen smaller reductions in tumour volume or stable disease.
So what does all this mean?
Well to me (as a layman), today’s Phase 1a data release further rubber stamps the scientific efficacy of the preCISION platform, and strongly suggests it can be applied across a broad range of other chemotherapies and new, more potent cytotoxins - together a multi $bn per year addressable market.
In fact AVCT's next drug candidate AVA3996, a FAP-activated proteasome inhibitor, is slated to enter clinical trials in 2024.
Plus, Avacta is now hoping to accelerate the start of AVA6000’s pivotal Phase 2 efficacy study into 2024. Although firstly it needs to complete its ongoing Cohort 7 program, alongside the separate fortnightly dosing study in the US.
CEO Alastair Smith commenting: "The data show that the preCISION modification is cleaved specifically by FAP, and not by other human enzymes. The ability to target the activation of a toxic drug to the tumour tissue also makes it possible to consider using even more potent cytotoxics that could not previously have been administered for safety reasons."
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