Chris Heminway, Exec-Chair at Time To ACT, explains why now is the right time for the Group to IPO. Watch the video here.
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thanks folks, some great points here.
Good post. I can add that apparently the cleaving enzyme is more prevalent in human tumours than it is in mouse tumours. So good chance of replicating success but as they often quote......This is science....so not proven till it’s proven
Avacta have some good research partners " close collaboration with Professor William Bachovchin "
"FAP is a serine protease selectively expressed on the surface of stromal cells surrounding most tumors of epithelial cell origin; but it is not present in most healthy tissues. Activation of the prodrug by FAP directs the proteasome inhibitor to selectively kill the tumor and its supporting stroma. The resulting depletion of the stroma may also lead to activation of the immune system to kill the tumor by relieving the immunosuppressive effects of stromal cells. The released proteasome inhibitor has been designed to inactivate with time so as to further limit exposure of normal cells and tissues to its cytotoxic effects. The lead compound has been demonstrated safe and effective in animal models of pancreatic cancer and multiple myeloma."
Other Avacta programmes
AVA004 | PD-L1 Checkpoint Inhibitor
https://avacta.com/therapeutics/pipeline/
Recent paper https://pubmed.ncbi.nlm.nih.gov/32987122/
Characterization of a single chain variable fragment of nivolumab that targets PD-1 and blocks PD-L1 binding
AVA004 | PD-L1 Checkpoint Inhibitor
https://avacta.com/therapeutics/pipeline/
https://gsbs.tufts.edu/facultyResearch/faculty/bachovchin-william/research
https://gsbs.tufts.edu/facultyResearch/faculty/bachovchin-william/publications
To this very question don't forget this little beauty from the Q & A in the 2019 Accounts:
How confident are you that the phase
I clinical trial for AVA6000 will be successful and will the
COVID-19 pandemic cause significant delay in starting the trial?
The animal data are very compelling. The improvement in therapeutic index of doxorubicin in the form of
the AVA6000 pro-drug is not marginal, it is black and white. This gives us
a high level of confidence that we
will see these data reflected in
a positive phase
I study in cancer patients. We will conduct this clinical trial
in the UK and are working now to complete the stability studies that will finalise the regulatory package
and allow us to submit this to the MHRA.
A reduction in staffing levels within our contract manufacturing
and clinical operations partners has not caused
a significant delay to date but this may mean that there
is
a short delay in the regulatory submission for the AVA6000 clinical trial to the MHRA into Q3. Many
clinical trials have been halted due to the pressure on clinicians and hospitals during the current COVID-19
pandemic. We do not expect there to be
a significant delay but it is prudent to assume
a short delay in
starting the AVA6000 phase I study perhaps into early Q1 2021. This also means that the associated costs
are delayed, and there is sufficient cash on the balance sheet to complete the phase
I trial as well as
progressing our other programmes.
"HIGH LEVEL OF CONFIDENCE"
Ps great to see £2 again. hopefully we will build on from here!
I would assume so, I don't see avacta having a medical affairs department and aren't recruiting for one. With there only being a need for phase II trial to gain MA, one would expect a medical team in place to start building relationships with therapy area experts, congress support, insight gathering etc..
Any thoughts, if successful, how much it might expand TAM AS was talking about new categories of person who could take it - I would guess that might about double TAM and then apply a further multiplier to the upping of dosage - I believe he said 3 x. So in best case scenario a TAM over 6 billion
I'm assuming that the drug is activated, that this activation occurs predominantly in tumour cells and that dox side effects are all proportional to systemic levels (amount in circulation (sort of).
If it acts in humans as it does in mice then the current market of £1B+ per year for dox is there - licence to big oncology player and save costs of promotion.......
Thanks RD - I think it was about 1/16 as toxic wasn't it in mice - which suggesting minimal leaching is repeated in humans
Regarding your last point, what I would say is that the vasculature of mice and humans can be quite different in different tumour sites, so the seeping of drug once tumour shrinkage occurs may pose a risk.
No I don't think it is
The main worry has to be cardio toxicity - that is the problem this drug is meant to overcome.
The pro drug is intended to become doxorubicin inside cancerous cells. Cardiac cells uptake dox plus they have high mitochondrial load hence the issue of toxicity . If the pro drug first whatever reason is activates in cardiac cells you will get toxicity. If it fails to get activated in cancerous cells you will get lack of activity. The animal work (mammals) looks promising in both these respects. Unite that dox cardio toxicity is cumulative so even the first dose currently needs to be restricted - the troponin measurements (marker of cardiac damage) will be available at phase 1 but a safety monitoring committee is likely to be looking at those very closely - again animal models looking good.
The other area would be if you get leeching of dox out of cancerous cells and the dynamics of this. Doesn't seem to be a big issue in mice but not a lot of info available.
@ZeroBagger, correct, it is TMAC that combines pre|CISION™ and Affimers. Excellent explanation from Sir Al yesterday.
GLA
Happy to be corrected but I don’t think AVA6000 is based around Affimer tech?
Bringing blockbuster drugs back on patent at minimal cost must be like the biggest windfall for the majors and although great I somehow think the rewards look like being disproportionate but this observation perhaps does not apply if the the prodrugs do not sell for more than they cost now. A possibility of a rule change should be avoided because of them not requiring phase 3 and could be fair because more beneficial applications of the reworked drug becomes possible with higher doses and full remissions meaning a possible saving to society due to less total treatments and a productive citizen returned.
Agree with this. The lack of requirement for a phase III is very positive. In regards to funding, I don't suspect that to be an issue. For me it is all about whether the precision technology can be replicated in humans. There are plenty of technologies out there which work great in mice but can be hard to replicate in humans with safety being the key concern. We don't know how the human immune system will react, nor we do we know about the potential of anti-drug antibodies for this molecule and the impact of them.
A lot resides on the results of the phase I, if negative, will probably set the company back a couple of years, if positive, I honestly believe the company will be utterly transformed.
What I don't know much about is the prospect of another company aquiring the rights to their technology or buying the company out completely. I can't see why big pharma would want such a competitior if the tech works
The chances of clinical trial success of AVA 6K are complicated to predict. A large proportion of failures in clinical trials appear to be down to factors which it should be pretty well protected from - including lack of efficacy, high side effects, poor trial design and running out of funding. And of course the concern of failure at Phase III - which afflicts nearly half of all trials that get through Phase II - is not relevant to us.
I think the main concerns are the effects of affimers in humans and whether the impact seen in mice will be repeated in humans (mind you the impact was so high that even half of it would be profound)
As to consequences of success, clearly if it works it is potentially not just about taking over the Doxa market but expanding both through greater dosing and ability to use it on groups who can't have Doxa due to age or comorbidities. So the TAM might be 5 or more times more than what it currently is.
Another effect is that is materially derisks the rest of the affimer/PreCision pro drug therapy pipeline.
Thoughts welcome.
For a variety of reasons, including insufficient funding, the failure rate at Phase III is high - nearly 50%. By not needing that stage AVA I gather