The latest Investing Matters Podcast with Jean Roche, Co-Manager of Schroder UK Mid Cap Investment Trust has just been released. Listen here.
A good, but long, review of ADC toxicity:
Mechanisms of ADC Toxicity and Strategies to Increase ADC Tolerability
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9913659/
"...escalating AVA6000 doses from 80mg/m2 (51 mg/m2 doxorubicin; molar equivalent, 0.675) to 385 mg/m2 (260 mg/m2 doxorubicin equivalent)."
Anyone else spotted Avacta's obligatory mistake? Having told everyone that 80mg/m² of AVA6000 was equivalent to 54mg/m² of doxorubicin from the start they have put 51mg/m² in the abstract. Again, Avacta still operationally useless.
Free Ribena bottle with every error identified.
Correct. Poster will have tables, graphs, bells, whistles and everything.
Seems a bit of a mess. Having been involved in website maintenance myself, I know that it should be straightforward: you have a development (internal) server and a production (internet-facing) server; you play around on the development server until everything is working as you want it to; and then you copy everything over (publish) to the production server.
Doesn't seem to be much, if anything, new here.
Abstract:
Background: AVA6000 is a peptide drug conjugate, consisting of a peptide moiety that is specifically cleaved by FAP in the TME that is bound to doxorubicin. FAP is selectively overexpressed in many solid tumors. The peptide moiety linker (pre|CISIONTM) prevents cellular entry of doxorubicin unless cleaved by FAP, thus enabling targeted delivery of doxorubicin to tumors.
Design: The safety, PK and preliminary efficacy of AVA6000 was studied in a first-in-man, multicenter dose escalation phase I trial. AVA6000 was administered intravenously q3w using a standard 3+3 design in patients with locally advanced or metastatic solid tumors reported to be FAP-positive. PK (AUC) based dosing was implemented to calculate maximum cycles of AVA6000 with the cumulative limit of 550 mg/m2.
Results: Forty patients (median age 65 years, range 30-79), with median 3 prior lines of therapy (range, 0-7) received escalating AVA6000 doses from 80mg/m2 (51 mg/m2 doxorubicin; molar equivalent, 0.675) to 385 mg/m2 (260 mg/m2 doxorubicin equivalent). Tumor types included soft tissue sarcoma (30%), colorectal cancer (27.5%), pancreatic cancer (20%), cancers of the biliary tract (7.5%). The safety profile was favorable, the most frequent adverse events (any grade) being fatigue (50%), alopecia (42.5%), and nausea (32.5%), with rare grade 3-4 hematologic toxicities of neutropenia (7.5%), anemia, thrombocytopenia, and WBC decreased (5% each). Grade 3 non-hematologic toxicities included mucositis, fatigue and hematemesis (n=1 each). No grade 4 non-hematologic toxicities were reported. 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). AVA6000 distributes rapidly with a t1/2 of 45 min. The Cmax of released doxorubicin was reduced as compared to standard dose doxorubicin (range 78-93% reduction) across dose cohorts. Tumor biopsy data demonstrate concentration of doxorubicin in the TME of mean 860 ng/gm (range 76-2310 ng/gm, n=9). In contrast, blood samples taken with the biopsy demonstrate a circulating free doxorubicin of 8.3 ng/ml (range 2.4-15.9), indicating concentration of doxorubicin in the tumor relative to plasma. Using RECISTv.1.1, one PR (-65%) with duration of 6 months was observed in a patient with undifferentiated pleomorphic sarcoma at 160 mg/m2, and a mixed response in a patient with angiosarcoma (SLD -22%) at 200 mg/m2. The disease control rate was 50%, at 12 wks. In each case, SD > 4 months or PR was associated with high FAP enzyme activity in the on-study tumor biopsy compared to observed disease progression as best response (n=6).
Conclusions: AVA6000 delivers high concentration of doxorubicin to the TME relative to plasma which results in antitumor activity in tumors with high FAP activity. A q2w dose escalation arm is ongoing.
And "Cleave – remove" ..... ?
Session PO.CT01.02 - First-in-Human Phase I Clinical Trials 2
CT188 / 16 - A Phase I trial of AVA6000, a Fibroblast Activation Protein (FAP)-released and tumor microenvironment (TME)-targeted doxorubicin peptide drug conjugate in patients with FAP-positive solid tumors
https://www.abstractsonline.com/pp8/#!/20272/presentation/11478
Abstracts are under embargo and will be released at 3:00 PM ET on Friday, April 5. So should appear here 8pm BST..?
And so it starts...
Aye, Ribena has that effect. Makes the patients a bit fruity though.
Question to GoSushi:
You say the TG group (and, for clarity, I am not a member of that or any other PI group) kept the details of their representatives' meeting with Avacta to themselves, and that that is wrong, so do you also think it wrong that fund managers such as Gervais Williams at Premier Miton also keep the details of their meetings with Avacta to themselves?
i see you're all over this like a smear of ****. what a sad way to live.
Maybe you should contact AS to complain then rather than moaning on here.
Not sure Strangy whether you're arguing that AS shouldn't interact with that particular group of investors or whether every interaction with investors, be they PIs or IIs, should be made public?
Whichever it is you are arguing, you probably need to take a few iminutes to sit quietly and consider what you are really trying to say.
Why not Foreverwaiting?
Before the December presentation and Q&A I lodged a series of eight questions with IMC and emailed them to AS, stating that I had been frustrated with previous Q&As because only a few of the questions got answered.
He responded: "Thanks for your email. Those are all excellent questions. We will get through as many as we can online and I will do my best to answer them all one way or another."
My questions were Q2 to Q6 in the Q&A. The ones not specifically answered were two about the trial design (covered in the presentation) and one about profiling side effects (overlapped with the answer to my question about investigating genetic typing - the 'new intellectual property' answer).
I had been in contact with AS a few times prior to sending that email. We've never met but I volunteered proof in my introductory email that I am a shareholder. I think he would require such proof before engaging in correspondence, otherwise the likes of our own friendly sealion would be forever bombarding him with questions. What level of share ownership he would deem necessary I don't know but I, alone but with a relative even more so, am a substantial LTH.
🤔 Strangy, are you saying that AS shouldn't interact with shareholders?
End of tax year selling to crystallise gains/losses and get cash ready to invest for next year's ISA and pension.
Well I'm extremely doubtful that Avacta would be using AI themselves inhouse and we've had no announcement of an agreement with another company to use AI, so... Maybe it's a project from a secret agreement. Or maybe AI isn't being used but something else is. My money's on a diagnostic biomarker test for each prospective patient.