Member Info for CTSFO

https://*********************/companies/uk/other/avacta-group-plc/research/trinity-delta/trinity-delta-lighthouse-avacta/33_c9f2ba7a-9abd-4511-b8f2-444d0e3dd158

Good Luck Everyone

FUD FOR ICECOOL ONLY.!!!

P1a study only. Remember the CoViD LFT? Can’t bring anything to market.

EVERYONE ELSE:

👌✊🏻👏👏👏🤑🤑🤑🤑

Thanks both.

Happy to be corrected here.

This is incredible news from the Orphan Drug Designation for AVA6000 and STS. Will they be able to hybrid (my choice of phrase, sorry) a P2+3 trial to get AVA6000 to market quickly?

Don’t listen to old trader. I’ll give you 56p.

MATML74 THANK YOU FOR THE CORRECTION 🙏

Sorry for the inadvertent FUD. I hope Avacta give the explanation about the cardiac event in an RNS supporting the presentation, as they did in science day. I hope it doesn’t mislead anyone else. Doxorubicin without cardiotoxicity. Holy grail.

Thank you, appreciate this.

Matml74

Good morning, do you have a link to the science day this event was mentioned at please?

Thanks

It’s incredible news. Simply incredible. The platform works.

Matml74: I will look at the science day. But I took DLT in

“Two DLTs were observed of grade 2 cardiac failure (120 mg/m2; LVEF decrease 61 to 39%) and grade 4 neutropenia/ thrombocytopenia (200 mg/m2)”

To mean:

“Dose-limiting toxicity (DLT) Toxic effects that are presumably related to the drugs that are considered unacceptable (because of their severity and/or irreversibility) and that limit further dose escalation. DLTs are defined before beginning the trial and are protocol specific.”

Suggesting the myocardial dysfunction was drug related. A big error if Avacta have got it wrong on their poster. Excellent news if you’re right tbh.

40 patients, spread across different cohorts, doesn’t fit well blended together and presented as simple percentages. The treatment and dataset of each patient can be presented. It would be very helpful to know the dose to cardiotoxicity timescale, for example.

Evening BV. From the 3rd Feb 2022 RNS:

“Avacta Group plc (AIM: AVCT), a clinical stage oncology drug company and developer of powerful diagnostics based on its innovative Affimer® and pre|CISION™ platforms, announces that the first-in-human Phase I trial (ALS-6000-101) of AVA6000 Pro-doxorubicin will advance to the next dose cohort following a positive review of the safety data from the dosing of the first cohort.

Avacta's Safety Data Monitoring Committee (SDMC), comprised of clinicians currently recruiting patients, has completed its review of the safety data from the first cohort dosed with AVA6000 at 80mg/m2 in the ongoing Phase I trial. Following this review, the SDMC has recommended that the clinical trial continues as planned and escalates to the next dose of AVA6000 at 120mg/m2.”

So my thought was if cardiotoxicity had occurred immediately, or very soon after, the C2 120mg/m2 trial; could it have been taken as the MTD at that point? But because it didn’t, the subsequent cohorts proceeded. Agree no MTD found. This one off incident was just ‘bad luck’.

You were saying? 👌

I posted without seeing DLT’s post. Please don’t think it’s a criticism of his post. From what I’ve seen I’d choose AVA6000.

Without wishing harm on anyone, thankfully it looks like the cardiotoxicity at 120mg has been a late event. If it had occurred immediately, would this have been the MTD? Or would further, more cautious, dose escalations have taken place.

And we’ve got to remember this is a P1a study. Powered and designed for safety only. Everyone has to be very very careful extrapolating these results to prove efficacy. It’s reassuring that efficacy is being suggested, but not proven. In saying that, another point worth thinking about is that all of the patients have already had other chemotherapies, if I’m reading it right. A median of 3 drugs? So cancers already effectively selected to show drug resistance. So if there has been an effect here, it’s impressive.

Morning all.

“ Two DLTs were observed of grade 2 cardiac failure (120 mg/m2; LVEF decrease 61 to 39%) and grade 4 neutropenia/ thrombocytopenia (200 mg/m2.”

Not the best constructed sentence.

1 patient (only one thankfully) has had a cardiotoxic response. This occurred in the second cohort, announced to start back in Feb 2022.

There’s going to be interest in the time between dose and the cardiotoxicity occurring. It’s well known that the cardiac damage can be delayed with doxorubicin. Hopefully the ongoing surveillance of the participants will show this is a very rare occurrence.

OR. If not very rare, it is balanced by far greater tumour cytotoxicity being associated with the significantly higher free doxorubicin in the TME.

(LVEF Left Ventricular Ejection Fraction. The relationship between the end diastolic volume (full heart) before ventricular contraction, to the end systolic volume (‘empty heart’) at the end of a normal contraction.

The paper:

https://www.sciencedirect.com/science/article/abs/pii/S0009898119320674

Evening. Reference paper to follow.

“ Remarkably, some types of chemotherapy-induced cell death exceed the pure antineoplastic effect. Anthracyclines, a widely used class of chemotherapeutic agents, are known to induce an immunogenic cell death (ICD). Anthracycline-treated tumor cells release immunogenic damage associated molecular patterns (DAMPs) such as HMGB1 or calreticulin which stimulate antigen presenting cells and promote a T-cell response against tumor cells [5].”

AVA6000 will only work in FAPalpha rich TME / tumours. We know this. Could tumour cell death biomarkers be used as a way of assessing / proving tumour death is taking place? Some trials are taking place on radiotherapy of cervical cancer and seeing if there is an association with long term survival. I’m wondering if we’ll see something similar being trialed with the AVA drug family?

🙏👏👏👏👏