Member Info for marik

In pre-clinical trials AVA6000 (the pro-drug form of Dox) was given at 6-fold higher concentration than the MTD. On interaction with FAP alpha the pre|Cision substrate is removed and the Doxorubicin (“warhead”) can be released in the TME. Following delivery, Doxorubicin levels in the heart was similar to the MTD, yet 18x higher in the tumour. The total amount of Doxorubicin in the plasma was also less. These lower levels in the plasma are important as the circulating off-target Doxorubicin is less than the conventional chemotherapy. This is despite the amount of FAP alpha present in the mouse plasma being higher than in humans. The pre-clinical trial data verifies that targeting was very good.

AVA6000 (phase 1a) clinical trial (first in human) commenced with first patient dosed around 11th Aug 2021. Each cohort will have 3 patients which in theory can start at any time. There are approx. 3-4 cohorts approx. 15-20 patients. Each cohort will run a standard DLT feedback with escalating doses (maximum of 6 cycles). Trials are staggered with cohort 1 and 2 potentially overlapping, and cycles 3/4 data (zero DLT ) providing enough to trigger the next cohort start. The standard dose for Doxorubicin, is approx. 60mg/m2 for a maximum of 6 cycles.

The accumulative maximum dose in cohort 4 is around 1600mg/m2 which is equivalent to 4.5x greater than the current MTD of Dox. Data at end of Q421/Q122 will be approx. 1.8x MTD. Remembering that there will be much less Dox in the circulation and a higher concentration in the tumour. One would expect it to show positive PKPD data and in doing so, it underlines the pre|Cision platform used by Avacta and opens up the drug pipeline for the future and will significantly impact the company valuation.

Looking forward to the initial PK data which is 6-8 weeks away (end Q421/ early Q122) which will validate the pre|Cision platform, dramatically increase the company valuation with the potential to transform the chemotherapy market.

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Thanks Poirot and gmcc, really useful. News on the Velcade prodrug AVA3996 will be announced at the end of this year and the future pipeline will include pre|Cision forms of Paclitaxel, Oxaliplatin and Gemcitabine.

[For new comers:] The highly specific pre|Cision based prodrug AVA6000 is based on substrate and drug (doxorubicin) conjugate being cleaved during interaction with FAPa present on the cancer activated fibroblast cell surface (CAFs). Delivery of doxorubicin (dox) at MTD of 2mg/kg (in mice) resulted in equivalent levels of dox in the heart and tumour. AVA6000 delivery at 12mg/kg (in mice) resulted in 18-fold higher doxorubicin in the tumour compared to the heart, increased the survival rate after 60 days and dramatically decreased tumour volume size.

AVA6000 in non-disease subjects and tissue proved a higher ratio of pro-Dox:Dox, indicating a very low level of background FAPa. Work from the Bachovchin Lab shows that plasma FAPa levels are ~15x higher in mice than in humans. Similarity between species of FAPa hydrolase domain (ClustalW analysis) gave ~93% (Human:Mouse) and 100% (Human:other primates). Baseline distribution of FAPa and imaging studies confirm that the TME has selectively higher distribution of FAPa. FAP-specific small-molecule inhibitors used for imaging gives differential distribution of FAP in humans with a high tumour-to-background ratio.

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I am part of a majority on the LSE Avacta bulletin board that is fed up with trolls. In unity with my fellow shareholders, I have filtered:

Ndn71 RorkesDrift coolfree wyndrum AgentB

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We as supportive shareholders of Avacta, will add further Usernames of other trolls to this list, if required. But: we will not let discussions over “troll-blocking” clog the bulletin board, needlessly.

I have taken it upon myself, in union with my fellow shareholders, to not respond AT ALL to the baiting of the trolls in response to this Signature.

To LSE admin reading this: I would rather be banned than continue to read the disgusting drivel and slander, on an hourly basis, from the trolls named above - that you have hitherto failed to police. Get a grip; do your job.

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"These numbers are decided by working out the statistical power..."

100% agree with you Matml74, the numbers are guided by the statistics and with input from the FDA. You are also right to question the 770 patients and I also questioned it as I'm not sure if they will have enough data and whether they had enough patients enrolling.

GLA

The Pfizer trial has an estimated enrolment of 3000 participants and this number will have been arrived at by the FDA and Pfizer. For Synairgen it was initially >900 participants and was then cut back by the FDA to ~600. It's more about the number that the FDA and the pharma company estimated enrolment which is difficult to cross compare unless they are very similar. For reference; one is inhaled the other is in tablet form, the stage of intervention and mechanism of action are different and the data from Synairgens other recent trials backs SNG001 for successful phase 3.

Pfizer certainly have form for overselling what turns out to be underwhelming results i.e. the vaccine. With Synairgen being broader anti-viral I don't think this is a significant competitor. However, there are two very positive take home messages; a) Pfizer and Merck now trying to run full steam at the therapeutics as opposed to vaccine market and b) Pfizer increased their market cap on open to the tune of >$20B. Indicating that the market size is substantial from investors point of view. Considering that SNG001 is not a direct competitor I think that both of these items point to Synairgen having a potentially bright future ahead. Especially with mutations and new VoCs.

There are two trials that this possibly refers to, but most likely this one (1) as the primary end points refers to "proportion of participants with COVID-19 related hospitalization or death from any cause". I am very surprised that they only provided data from 770 patients (out of a total of 3000) given that the last patient is meant to be dosed in approx 1 month. Was there a lack of patients? If so, I presume it indicates that they fall short of the total required and are therefore pushing for EUA in the hope that the FDA passes it.

1. https://clinicaltrials.gov/ct2/show/NCT04960202?term=NCT04960202&draw=2&rank=1

Should ask under this thread if anyone knows which drug it is? I assume they finished much earlier than expected because they couldn't find enough patients?

This is quite interesting. I only know of one drug off the top of my head that Pfizer are working on for Covid that would have data around now. My thoughts are that the ~750 patients implies that they couldn't find enough patients. Does anyone know which drug?

Afternoon Ian,

Could you please add me for after hours today please. Could be wrong, but there is a mismatch in the volume and price (hi-lo).

Thank you and GLA LTH.

@Icecool I have to agree: "Avacta test should be high on the list"

@Okehurst1, I forgot to add. Post application, October 31st was the date for completion of the validation process and by which the COVID-19 test must have passed the minimum performance thresholds.

This CTDA discussion came up from another board and I thought I'd share. The application process (1) looks straight forward, but the desk review is not:

a) check for completeness
b) initial review by a scientific advisor
c) peer review of above
d) presented to the Desktop Review Assurance Group

I presume that DRAG (aptly named?) meets once a week on Thursdays (judging by the approval dates of the three approved tests). There's likely to be a big backlog of tests and a lot of applications. I would expect applicants to receive feedback on Thursdays/Fridays. There could be a gap between approval news for two companies by a week purely down to capacity of the DRAG.

One very big positive to take from all of this, is that the likes of Surescreen and Innova will be side lined in the coming months as the better quality tests will start to take a hold. That is the intended purpose of the exercise. Once the first lateral flow test passes the CTDA Regulations, you have to ask the question why would anyone chose one of the temporary protocol tests? My view is that the temporary tests will only be useful if there is a manufacturing capacity shortage of CTDA approved LFT tests.

Good luck.

1. https://www.gov.uk/guidance/covid-19-test-approval-how-to-apply

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I am part of a majority on the LSE Avacta bulletin board that is fed up with trolls. In unity with my fellow shareholders, I have filtered:

Ndn71 RorkesDrift coolfree wyndrum AgentB

I suggest that everyone reading this, who hasn't already filtered these names, clicks on 'Filters' and then copies and pastes in the entire line of Usernames mentioned above.

We as supportive shareholders of Avacta, will add further Usernames of other trolls to this list, if required. But: we will not let discussions over “troll-blocking” clog the bulletin board, needlessly.

I have taken it upon myself, in union with my fellow shareholders, to not respond AT ALL to the baiting of the trolls in response to this Signature.

To LSE admin reading this: I would rather be banned than continue to read the disgusting drivel and slander, on an hourly basis, from the trolls named above - that you have hitherto failed to police. Get a grip; do your job.

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@Okehurst1, I believe the cut off for all applications was 31 Aug and Omega will have submitted before then. As with many others who submitted at the same time, they will have assumed that approval would have been conferred by 1 November. My view is that approval news for Omega and Avacta will be announced at around the same time. The application process (1) looks straight forward, but the desk review is not:

a) check for completeness
b) initial review by a scientific advisor
c) peer review of above
d) presented to the Desktop Review Assurance Group

I presume that DRAG (aptly named?) meets once a week on Thursdays (judging by the approval dates of the three approved tests). There's likely to be a big backlog of tests and a lot of applications. I would expect applicants to receive feedback on Thursdays/Fridays. There could be a gap between approval news for two companies by a week purely down to capacity of the DRAG.

I agree that Medusa19 may have made EU HUA application earlier and therefore Avacta could be a little ahead.

One very big positive to take from all of this, is that the likes of Surescreen and Innova will be side lined in the coming months as the better quality tests will start to take a hold. That is the intended purpose of the exercise. Once the first lateral flow test passes the CTDA Regulations, you have to ask the question why would anyone chose one of the temporary protocol tests? My view is that the temporary tests will only be useful if there is a manufacturing capacity shortage of CTDA approved LFT tests.

Good luck.

1. https://www.gov.uk/guidance/covid-19-test-approval-how-to-apply

An observation:

“The new CTDA Regulations required all suppliers of COVID-19 tests to submit information regarding their products for desktop review prior to 31 October 2021 if they wished their products to remain on sale in the UK after this date.”

This statement refers to *all* suppliers and not just Omega and, 31 October 2021 is the last date on which you can sell your test prior to the CDTA regulation coming into force on 01 November 2021. For reference, Novacyt's similar statement:

“Only validated products, or products on the temporary protocol, can be sold in the UK after 31 October 2021”.

Mart, we've just exchanged some tweets and I still think he's a great guy. (:0)

In addition see the following image outlining "FAP-high" tumours.

https://twitter.com/marik_investor/status/1455521683763236866

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I am part of a majority on the LSE Avacta bulletin board that is fed up with trolls. In unity with my fellow shareholders, I have filtered:

Ndn71 RorkesDrift coolfree wyndrum AgentB

I suggest that everyone reading this, who hasn't already filtered these names, clicks on 'Filters' and then copies and pastes in the entire line of Usernames mentioned above.

We as supportive shareholders of Avacta, will add further Usernames of other trolls to this list, if required. But: we will not let discussions over “troll-blocking” clog the bulletin board, needlessly.

I have taken it upon myself, in union with my fellow shareholders, to not respond AT ALL to the baiting of the trolls in response to this Signature.

To LSE admin reading this: I would rather be banned than continue to read the disgusting drivel and slander, on an hourly basis, from the trolls named above - that you have hitherto failed to police. Get a grip; do your job.

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@Ophidian, I've seen data presented on distribution of FAP throughout the body in very low quantities but high upregulation in tumour sites (especially those cancer types pointed out by Alastair).

@Ophidian, has anyone presented any evidence to suggest that it is in high concentrations elsewhere?

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I am part of a majority on the LSE Avacta bulletin board that is fed up with trolls. In unity with my fellow shareholders, I have filtered:

Ndn71 RorkesDrift coolfree wyndrum AgentB

I suggest that everyone reading this, who hasn't already filtered these names, clicks on 'Filters' and then copies and pastes in the entire line of Usernames mentioned above.

We as supportive shareholders of Avacta, will add further Usernames of other trolls to this list, if required. But: we will not let discussions over “troll-blocking” clog the bulletin board, needlessly.

I have taken it upon myself, in union with my fellow shareholders, to not respond AT ALL to the baiting of the trolls in response to this Signature.

To LSE admin reading this: I would rather be banned than continue to read the disgusting drivel and slander, on an hourly basis, from the trolls named above - that you have hitherto failed to police. Get a grip; do your job.

..........

@Oph, we know that FAP-alpha is present in very low concentrations i.e. background FAP levels. The vast majority of the expression is within the tumour. See my post earlier today.

..........

I am part of a majority on the LSE Avacta bulletin board that is fed up with trolls. In unity with my fellow shareholders, I have filtered:

Ndn71 RorkesDrift coolfree wyndrum AgentB

I suggest that everyone reading this, who hasn't already filtered these names, clicks on 'Filters' and then copies and pastes in the entire line of Usernames mentioned above.

We as supportive shareholders of Avacta, will add further Usernames of other trolls to this list, if required. But: we will not let discussions over “troll-blocking” clog the bulletin board, needlessly.

I have taken it upon myself, in union with my fellow shareholders, to not respond AT ALL to the baiting of the trolls in response to this Signature.

To LSE admin reading this: I would rather be banned than continue to read the disgusting drivel and slander, on an hourly basis, from the trolls named above - that you have hitherto failed to police. Get a grip; do your job.

..........

@Oph, we know that FAP-alpha is present in very low concentrations i.e. background FAP levels. The vast majority of the expression is within the tumour. See my post earlier today.