Member Info for marik

@travel_light, the doctor running the trial (and the team) would make that call based on the prognosis of the patient.

Let's assume that the pre-clinical trial is replicated in humans, then the amount of doxorubicin targeted at the tumour will have an 18x greater concentration of doxorubicin targeted at the tumour as opposed to systemically. I will be intrigued to see the data from phase 1a.

Positive data from phase 1a PK results will imply that other drugs will then become part of the Avacta therapeutics pipeline. Following in the footsteps of AVA6000 we could well expect the selection of the Velcade prodrug candidate (AVA3996) before the end of the year and further pipeline to include the pre|Cision forms of Paclitaxel, Oxaliplatin and Gemcitabine. With the reduced timeframe, expense, exceptional pre-clinical data, so far positive news (i.e. no negative news from NCT04969835) and the diagnostics division revenue from the UK and abroad to underpin the costs of future clinical trials, Avacta is in my mind derisked as an investment.

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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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(3/3)

Even though in this phase 1a trial the dosage administered will provide an effectively 54mg/m2 (0.68 of 80mg/m2), the prodrug will continue to circulate in the system until most of it will be targeted to the tumour site. If pre-clinical data (i.e. 18x) is replicated in humans, then the effective off-target to targeted distribution of doxorubicin could be very high i.e. a factor of 10 higher than what has previously been managed (before systemic toxicity kicks in). It will be exceptionally interesting to see the results from phase 1a.

Prodrugs that are precursors to previously approved drugs e.g. doxorubicin which are well documented and have already undergone various rounds of clinical trials can submit for NDA using at least some of the information required for approval coming from studies not conducted by or for the applicant. In doing so, this will heavily reduce the timeframe for approval and reduce the costs involved in bringing the drug to market.

(2/n)

Avactas AVA6000 (a prodrug) is in phase 1a first-in-human clinical trials and is formed from doxorubicin and a substrate referred to as pre|Cision. Cancer tissue has a surrounding tissue which is referred to as the tumour micro-environment (TME) and one of the activated cells Cancer Activated Fibroblasts (CAFs) present on their cell surface a Fibroblast Activating Protein alpha (FAPa), these CAFs can form as much as 90% of the tumour mass. In this #avct trial AVA6000 is given to patients with advanced and/or metastatic solid tumours, and on CAF cell surface, interaction between the FAPa and AVA6000 cleaves the substrate element from doxorubicin delivering doxorubicin locally to the TME. This targeted therapy allows for doxorubicin to target the malignant cells and is toxic to the cell through numerous intracellular pathways. The highly specific pre|Cision targeting of doxorubicin is what sets AVA6000 apart from other prodrugs using FAPa. From pre-clinical data, delivery of doxorubicin at the maximum tolerated dose of 2mg/kg (in mice) resulted in equivalent levels of dox in the heart and tumour. However, evidence points to AVA6000 being targeted to the tumour with an 18-fold higher concentration compared to doxorubicin. It also increased the survival rate of the mice after 60 days and dramatically decreased the tumour volume size. In pre-clinical experiments, post AVA6000 administration gave a much higher ratio of pro-Dox:Dox in non-disease subjects. This indicates that there is a very low level of background FAPa. Work from the William Bachovchin Lab shows that plasma FAPa levels are far higher in mice (~15x higher) than in humans.

There are several advantages with the pre-clinical model that points to a greater likelihood of success in humans. ClustalW analysis of FAPa hydrolase domain between species (Human:Mouse) indicated a high sequence identity ~93% similarity and a 100% between Human and primates. From studies on baseline physiological distribution of FAPa (i.e. non-diseased tissue) and imaging studies we can confirm that the tumour microenvironment has selectively much higher FAPa. FAP-specific small-molecule inhibitors are used for imaging and give differential distribution of FAP in humans and indicate a very high tumour-to-background ratio. FAPa expression is consistently high in many different cancer types especially when the prognosis is poor and later stages of the cancer including breast cancer (IDC, ILC and breast malignancies), head and neck cancers (oral squamous cell carcinomas), colorectal cancer, ovarian cancer and pancreatic cancers. These cancers are targeted (conditions/diseases) submitted in the CTA (see clinical trial NCT04969835).

1/n

Paul Hill (Founder PMH Capital Ltd) writes on LinkedIn

#AVCT #NCYT #ODX #ABDX #SBI

Following intense pressure from the media & travel sector, the government has vowed to cleanup the UK Covid testing industry.

As such, under new mandatory CTDA guidelines, all existing suppliers of PCR & RLFTs had to submit product data for a desktop validation to the UK Health Security Agency, if they wished to continue to selling from 1st November onwards.

Sure this is great news for holiday-makers, but unfortunately it appears the HSA didn’t have sufficient resource to fully implement the new rules in the stipulated timescales.

Meaning that as of today, there are only 3 fully approved tests (Roche Diagnostics, Life technologies & Clent Life Science) and another 48 (eg Oxford Nanopore) working off temporary protocols. Not surprisingly, this has impacted many firms including Avacta & Novacyt Group this morning.

In theory this should just be a timing issue, but for investors it does highlight how:

1) regulatory changes can affect even best-in-class covid screens.

And

2) competitive this part of diagnostics industry has become, despite still firing on full cylinders (see stats below).

For Avacta though, this UK suspension will not have a material impact its 2021 results. Instead it continues to focus on overseas opportunities for its leading AffiDX SARS-CoV-2 RLFT, including within Europe & elsewhere.

https://www.linkedin.com/posts/paul-hill-a5994116_avct-ncyt-odx-activity-6861214899620634624-Wyeo

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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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Another great post by Myles on twitter, well worth a read:

https://twitter.com/MylesMcNulty/status/1455245990492098568

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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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An excellent tweet by @TheEthicalTout on twitter and worth a read (1/5):

"Sanofi’s acquisition of Ablynx in 2018 is not lost on #AVCT. They paid 4.5Bn USD for Ablynx which has been working on Nanobody tech since 2001. Eight nanobodies had entered clinical development at the time of acquisition. It wasn’t until a year later Sanofi received FDA…"

https://twitter.com/TheEthicalTout/status/1455191795562946562

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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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For me, this certainly provides upwards momentum for the stock and increases my conviction for the company who have done an exemplary job. There are very few studies out there who provide such quality data, Mologic was commended by Professor Deeks for doing so and I can only applaud Avacta for taking similar steps.

I am under the impression that we will be discussing APAC agreements in the near future and can see that this paper would lend strength to future agreements and revenue streams. Furthermore the ease of use will certainly be underlining the self-test application submitted by Medus-19.

The future is looking very bright.

..........

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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In their recent independent [1] paper by Castan and colleagues [2] Affidx was clinically evaluated. The key take home points are as follows.

Using S1 protein in diagnostics is beneficial due to both functionality (ACE2 interaction) and structural accessibility. A total of 250 samples from consenting patients (of any age, gender, or race/ethnicity who presented at the test site) were tested with 150 negative samples and 100 positive samples and each test was in agreement with the ISO 15189. The testers were minimally trained operators, with little laboratory experience who received no previous training on use of the AffiDX® SARS-CoV-2 Antigen Rapid test. This was representative of true intended user setting. At Ct = 28, both specificity and sensitivity (S&S) are 100%. Avacta are also running a parallel study under review for publishing that delve further into comparative analysis versus a complete panel of LFDs.

In context; this study independently adds further data underlining the very high specificity and sensitivity of AffiDx, making this one of the most accurate LFTs in the world. The tests were in agreement with ISO 15189 and the testing included patients of any race/ethnicity. Which would be useful for APAC countries. Furthermore, the tests were used by minimally qualified individuals to replicate true to situation setting (ideal for HUA). The future study highlighted will no doubt provide additional quality data especially under comparative analysis and will differentiate the Affidx test compared to other companies.

The AffiDx covid-19 test at Ct = 28 gave a 100% S&S and was only marginally reduced (98%) at Ct = 30. The cost of RT-PCR tests can be prohibitively high in many countries across the globe for whom a *highly accurate* cheaper LFD would certainly help alleviate the spread of covid-19.

1. https://twitter.com/AvactaDx/status/1455143888117719042
2. https://www.medrxiv.org/content/10.1101/2021.10.28.21265544v1

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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.

..........

Excellent post Myles highly appreciated.

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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.

..........

Just a point to keep in mind is that the majority of the authors are from Hospital Carlos III in Madrid and two are from Avacta.

Their discussion is very important:

"The new AffiDX® SARS-CoV-2 Antigen Lateral Flow Test has shown a strong correlation with the RT-PCR correctly identifying all negative samples and showing no false positives 150/150 (100%). The system’s sensitivity for Ct =30 with 98/100 detected (98%) is equally interesting as Ct values =28 are considered to be responsible for the vast majority of infectious contacts under an epidemiologic point of view and the system reaches a 100% sensitivity for Ct =28 with 98/98 detected (100%)"

I'm encouraging other posters to share similar quality material. A very big thank you to the OP.

Great find. This was a meaningful post (PL75, Rorkes, Agent please take note). It should come as no surprise that affidx is a superior test. It's good to see it in review.

@Vegas22, could you please point me to one of your informative posts on Avacta (out of more than 2000)?

@Aldebaran. Nothing to see here I'm afraid.

Folks, I believe I am in the dog house with rorkes and ndn and for a good reason. I betrayed their trust; first the UT comments, then the health economics cap, then pre|Cision and TMAC comments, then the post statistics and now showing up the "significant news" comment. No wonder I have been blocked on twitter. I am rolling over and fetching as commanded and hanging my sorry doggy head in shame. I will make it up to them in the future. Woof woof. Woof woof.

In which case Timster, I must humbly apologise to you. Then it would seem that it would constitute significant news.

@RorkesDrift. Please wait your turn to deramp, I would prefer if ndn71 gave a Masterclass for now. Thank you in advance.

@Timster, if you are right, then it would new news, it would be considered as significant and not built into the price.

I am liking this, my two heroes having a discussion. I have my pen and paper out for todays Masterclass (yesterdays was excellent and very difficult to top).