Roundtable Discussion; The Future of Mineral Sands. Watch the video here.
Responding to the cause of FPs. FPs can be caused by non-specific binding or cross reactivity. Non-specific binding and cross reactivity are NOT the same.
Cytiva outline some solutions to False Positives that arise from non-specific binding.
https://www.cytivalifesciences.com/en/us/solutions/lab-filtration/knowledge-center/lateral-flow-assay-troubleshooting-and-how-to-switch-membranes
On a Cytiva Labroots Presentation in 2020, David Wilson (Avacta Commercial Leader) briefly spoke about the trade-off between Specificity and Sensitivity @ 36.20 mins https://www.youtube.com/watch?v=9sWbhA8nZR8
David stated explicitly the bias towards Sensitivity and NPV, as well making an implicit reference to Likelihood ratios "ideally high at both levels". It is important to produce a test that is "useful" across a broad range of disease Prevalence.
thanks,
Celtics.
The market is under-appreciating the LFT Clinical results due to inability to interpret. Will help the group to understand the Clinical significance using Predictive Values and importantly Likelihood Ratios used by Medical Statisticians. We can confidently say 98.96% Cumulative Sensitivity [95 TPs / (95 TPs + 1 FN)] up to and including CT Value 30 is robust. 19 Actual positives within CT 29-30, were ALL correctly identified as positive.
NPV = 99.02% [101 TNs/(101 TNs + 1 FN)]. PPV = 98.96% [95 TPs/(95 TPs +1 FP)], up to an including CT of 30.
Predicative Values like NPV and PPV are affected by Disease Prevalence. As Disease Prevalence lowers, a higher % of Positives are FPs. As Disease Prevalence increases, a higher % of Negatives are FNs. Manufacturing capacity potentially available to AVCT in UK has an initial Upper limit of 30M LFTs/month. Using that figure, with a Clinical Specificity of 99.02%, there would be 294,118 FPs/month. Currently, LFT positives are confirmed by PCR. If we price PCR at 50 GBP/test, that confirmation is 14.7M GBP/month cost. Economically, it’s better to take a second LFT immediately after, and the probability of receiving a First FP immediately followed by a Second FP is 0.0096% (101/102 x 101/102). This is GCSE Math (independent probabilities). From 30M tests/month, 2,884 persons would have a FP immediately followed by a Second FP.
Specificity and PPV is important when thinking about “a test to isolate”. Sensitivity and NPV is critically important when thinking about “a test to release /enter”. Test to release is important to safely allow a return to freedom, a Human need. Likelihood ratios (LRs) are NOT affected by Disease Prevalence. LRs inform us of the usefulness of a Test - https://www.uws.edu/wp-content/uploads/2013/10/Likelihood_Ratios.pdf. Positive LR = Sensitivity / (1-Specificity). Mathematically Positive LR is between 1 to 1000, with being as close as possible to 1000 indicating a more useful test and 1 useless. Negative LR = (1-Sensitivity) / Specificity. Mathematically Negative LR is between 0 to 1, with being as close as possible to Zero indicating a more useful test and 1 useless.
A Test to Release approach requires a very Low Negative LR i.e. as close as possible to Zero. Up to an including CT value of 30 AffiDX has Negative LR of 0.011. Whilst, on a larger sample set, Innova is claimed by Jon Deeks as having a Negative LR of 0.25 - https://twitter.com/deeksj/status/1326135461178388480
AffiDX shows evidence to support an effective and safe “Test to Release” approach in my opinion. I think the UK Gov’t will push Test to Release /Access to Enter using Professional Use only tests only with an auditable QR code/24 hr. Negative Test Certificate (using national pop up Testing stations). We’re seeing this in ongoing trials – Snooker, Nightclub, Wembley. In my opinion, this is the best way to safely keep prevalence low and not with home tests since sampling error increases.
Celtics.
Results disclosed today exceeded Avacta's self defined "high performing" test threshold.
https://avacta.com/how-diagnostic-test-performance-is-measured/
Sample Size - 200
1) Sensitivity (PPA) - how many of the positive cases are detected = 97.96%
= 96 True Positives / 98 Actual no. of Positives
2) Specificity (NPA) - how many of the negative cases are detected = 99.02%
= 101 True Negatives / 102 Actual no. of Negatives
3) Positive predictive value (PPV) - "how confident are we that a positive result is actually a true positive" = 98.97%
= 96 True Positives / (96 True Positives + 1 False Positives)
4) Negative predictive value (NPV) - "how confident are we that a negative result is actually a true negative" = 98.06%
= 101 True Negatives / (101 True Negatives + 2 False Negatives)
Note - Avacta have produced these excellent results where 65 out of 98 Actual Positives in the sample population had a CT value 26 to 30 (which is low viral load).
These results demonstrate why Mologic (GAD) offered capacity to Avacta instead of reserving that capacity for their own Antigen test. I think there is an exciting path ahead for Avacta and its Shareholders. Today was a significant milestone for Avacta, its employees and equally its manufacturing partners (GAD, BBI and Abingdon). Thank you!
Celtics.
In addition to Notice to Mariners 39, according to ship tracking /satellite monitoring, there are now two Vessels positioned at the Bulletwood-1 well site coordinates. ?Does this confirm the start of a re-entry well?
I am speculating that well log data collected and analysed from the initial Bulletwood-1 drilling has identified promising intervals that support further exploration /testing.
Recall this quote from the 2021 Exxon Investor Day by Neil Chapman, VP Exploration - “All of these wells confirm the presence of hydrocarbons and high-quality reservoirs and we are actively integrating the data to guide our future programme”
A re-entry well at the Bulletwood location is a significant pivot from the original plan disclosed by JHI Associates on 16th March. That plan outlined - Stena Carron maintenance, drill Koebi-1, then drill Jabillo-1. https://www.jhiassociates.com/media/bulletwood-1-well-results-and-jabillo-1-operational-update
I hope we receive some clarity from either Exxon, JHI Associates or Westmount in the coming days.
thanks,
Celtics
https://marad.gov.gy/wp-content/uploads/2021/04/Notice-To-Mariners-39-of-2021.pdf
Not sure what this means.
thanks,
Celtics.
Despite being uncommercial, Tanager-1 did find a successful trap and oil bearing reservoir at one interval; the Maastrichtian, and it has proved that oil has migrated far outwards and down-dip to the other discoveries on Stabroek.
The interims from WTE remind us also of the 50ft net oil pay discovered by Exxon at Hassa-1. I think the chance of success on Hassa-1 was lower than the other discoveries made on Stabroek, I recall an Investor presentation that John Hess conducted (i think it was with Bank of America in November 2020) where John was quoted saying that they were finding oil even where Seismic was "dim".
While Exxon have been extremely successful along that line in Stabroek (with reference to the slide from the 2021 Investor Day and seismic image), If you look at the basin map (JHI website), and consider the locations of Ranger-1, Tanager-1 and Hassa-1, I feel confident that the Canje block will eventually return a Commercial discovery at some point and that JHI is sufficiently funded to the extent to see it through to that eventual point.
I am particularly excited about Sapote-1, along with a DHI (direct hydrocarbon indicator) it is located down-dip of Haimara-1, and it is also targeting a deeper interval in addition to the Maastrichtian-Campanian interval.
JHI is also partnered with an Operator in Exxon that has already discovered 9B Barrels of recoverable oil in the basin and sees the basin potential being more than twice the discovered resource.
Oil & Gas exploration is inherently risky, but in terms of risk-reward WTE has a very good investment case at the current price point. At the end of 2021, after Jabillo-1 and Sapote-1 have concluded we may look back and think 11-12p/share what a steal.
thanks,
Celtics.
I added to my position this morning. I do expect an update inside 1Q21 and therefore this week.
This update could be -
1) AffiDX LFT CE marked by Mologic and/or,
2) AffiDX LFT CE marked by Avacta.
With reference to the RNS dated 8th February - Commercial Partnership with Mologic, Alistair explains,
"The partnership provides Avacta with a low risk route to CE marking our rapid antigen test during Q1 ahead of achieving our own ISO13485 accreditation".
thanks,
Celtics.
Thank you for sharing Bud.
This is quite an extensive evaluation of the Mologic rapid Antigen COVID-19 test.
For any comparison to the initial clinical evaluation data disclosed by Avacta to be meaningful, it is important to look at an apples for apples comparison.
Slide 4
There are 16 True Positive (TP) samples determined using the Cepheid PCR with a CT value < 25.
2x False Negatives are reported with CT value < 25 (out of 16 samples < 25 CT value).
Sensitivity PPA = 87.5%.
Slide 7
Non-meaningful to compare to the initial clinical evaluation data disclosed by Avacta. CT values up to 40, and the 112 True Positive (TP) samples are not broken out into CT value ranges.
Slide 8
Table with test evaluation using patient samples corresponding to CT value < 25. There are 108True Positive (TP) samples of which the Mologic test produced 11x False Negatives (FN).
Sensitivity PPA = 89.8%.
thanks,
Celtics.
LIMIT OF DETECTION –
Evidence shows that the lowest amount of S1 analyte an Affimer ELISA is able to detect is 10 times LOWER than the lowest amount of S1 analyte that an Optimer ELISA is able to detect and 100 times LOWER than the lowest amount of S1 analyte that an Undisclosed Antibody ELISA is able to detect.
Abcam Spike protein Antibody Elisa (S2 Subunit) – 2,700 pg /ml.
Undisclosed Spike protein Antibody Elisa (S1 Subunit) – 500 pg /ml.
Spike protein Optimer Elisa (S1 Subunit) – 50 pg /ml.
Avacta Spike protein Elisa (S1 Subunit) – 5 pg /ml.
https://www.abcam.com/covid-19-spike-protein-elisa-kit-ab274342.html?productWallTab=ShowAll
https://aptamergroup.com/aptamer-based-elisa-for-virus-detection-strong-potential-for-covid-19/
SIGNAL-NOISE RATIO –
The aim of a diagnostic is to have the lowest possible background noise with the highest possible optical density.
If the signal from the molecule of interest is lower than the background noise, the molecule of interest will be unrecognizable. Aptamer Group uses A.U (Absorbance units) as its measure of Signal-to-Noise ratio (figure 5 – Aptamer note).
Figure 5 demonstrates that an Optimer ELISA produces a higher signal to noise ratio than an Antibody ELISA at the same S1 protein concentrations, except at 50 pg /ml, which is the limit of detection an Optimer.
To produce a stronger signal requires use of a higher quantity of reagents, however that can lead to an undesirable increase in non-specific binding and higher background noise.
David Wilson refers to this tradeoff b/w Sensitivity and Specificity on a video seminar with Cytiva last year.
Qty. of reagents incorporated is influenced by the reagent molecular mass (Kda).
Antibody mass is ~ 150 Kda (reference Sigma Aldrich).
Optimer mass is 15 Kda (https://aptamergroup.com/optimer-therapeutics/).
Affimer mass is 12 to 14 Kda (https://avacta.com/diagnostics/what-is-an-affimer/).
Avacta make a reference to its small size lending to better signal to noise ratio within its “Flexible Functionalisation” note - https://avacta.com/diagnostics/affimer-diagnostics-key-benefits/
BINDING –
With reference to the Aptamer application note. Figure 1 shows excellent Affinity of Optimers towards SARS-COV-2 viral antigens – S1, S2 and Nucleocapsid. Figure 1b (S2 Optimer) suggests weaker binding versus Figures 1a (S1 Optimer) and 1c (NC Optimer).
This is indicated by the downwards slope (at 120s) for the S2 Optimer. A steeper slope downward indicates the antigen disassociates quicker from the capture reagent. A flatter slope means stronger binding. Standing out in Figure 4, an S1 Antibody is unable to bind to S1 in its trimeric form.
Viral proteins do begin to break down naturally during course of infection.
Avacta stated in an RNS that “Affimer reagents can detect both the intact virus particle and detached spike proteins which become separated from the virus particle during the development of the COVID-19 dis
Content to wait. We have 2 very high impact drills to be done this year with full carry by Total. Note, Sapote is very close to the source rock.
If one returns Commercial from Jabillo or Sapote, Exxon will very likely add another campaign for 2022 to progress exploration /appraisal, for which JHI will have 1 remaining carry by Total, and are fully funded for additional wells (wells not well).
Exxon, have indicated quite explicitly that Guyana is core to their business case and their intent to work at speed. Look at the number of drill ships that they will have contracted in 2H21 on Guyana exploration.
In my opinion, JHI's 4 well carry by Total is certainly the most appealing factor underpinning an attractive Risk-Reward ratio to WTE.
thanks,
Celtics.
Operational Update from JHI directly - https://www.jhiassociates.com/media/bulletwood-1-well-results-and-jabillo-1-operational-update
Provides guidance on drillings operations /plans /timelines.
There is also an updated basin map - https://www.jhiassociates.com/guyana-basin
thanks,
Celtics.
To provide some context of Valuation and M&A.
Reading through GenMark's 10K filing - https://ir.genmarkdx.com/static-files/093b5a24-3c0d-4377-8566-4079d136ac36
Page 35 -
2020 Full Year Revenue = $171.6M
2020 Gross Profit = $67.9M
2020 Operating Profit/(loss) = $(11.1)M
Page 36 -
2020 Operating Cash flow = $6.1M
From a GenMark Investor Presentation - https://ir.genmarkdx.com/static-files/5f594deb-584a-4ca8-bd81-590aa54ed5b0
GenMark offers a broad pipeline of COVID tests - Molecular, Antigen + Antibody.
This Company is to be acquired by Roche for $1.8B (subject to Shareholder approval). I repeat $1.8B.
In my opinion, Avacta will very soon have a market cap far in excess of 1.0B GBP following - Clinical Validation and CE marking of its COVID LFT.
Performance of the LFT has already been de-risked to some extent through the excellent initial Clinical Evaluation data. If that is repeated in the formal validation (which I expect), the UK Government will not doubt procure.
We have 3 publicly disclosed Manufacturing Partners for the LFT - BBI Solutions, Abingdon Health and Global Access Diagnostics. (I expect more to be announced shortly - Europe and South East Asia as Alistair has referenced).
Manufacturing is the limiting factor and Avacta is excellently positioned to continue looking at securing those additional partnerships and meeting the demand.
With the Intellectual Property (Affimer and Precision), existing Partnerships (Diagnostics and Therapeutics), and Therapeutics segment, this Company has significant upside potential from even the current base. I cannot emphasise that enough.
Good luck and try to stay objective!
Watch out for those people with an agenda. Remove the noise (filter button!) and try to think logically.
thanks,
Celtics.
A good small read for any new faces here.
https://www.sharebuyers.co.uk/shares/avacta-shares-going-for-growth-world-moving-rapidly-again/
thanks,
Celtics.
Do not be surprised by some profit taking.
Portfolio Managers at Institutions are often limited by the weight an asset becomes in portfolio, even if there is an unchanged positive sentiment in the asset held. Risk Management is very important.
For example, Baillie Gifford recently sold a portion of its holding in Tesla after it reached new highs, as there portfolio became increasingly exposed to Tesla.
In my opinion, attempting to value the Intellectual Property rights of the Affimer platform is very difficult and I am not competent to do so. Nonetheless, I do believe Avacta will soon have a market cap in excess of 1 billion GBP, with the following trigger points -
1) Achieving formal Clinical validation (with excellent results) and CE marking the LFT.
2) Award of a UK Government contract (in opinion I believe Avacta will take >=25% of the 8B tender amount.*)
*Note - Surescreen received a 500M GBP UK government contract. While, Avacta is partnered with multiple manufacturers that have been expanding capacity over many months.
Avacta's potential After-Tax FCF generation for a 2 Year LFT UK Government contract alone, that considers 5 GBP sell price per LFT, will see Avacta priced far higher than it is today today.
It is forward-looking expectations /guidance that underpin Valuation.
SARS-COV-2, as the leading scientists have indicated will unfortunately not go away, it will continue to Mutate and there will be a demand for Testing that will persist for many years.
To see a return of a functional economy with social interaction and global mobility, this can only happen with a joint approach of repeat vaccinations and frequent testing.
thanks,
Celtics.
Exxon have commented - back to back drilling
https://oilnow.gy/featured/exxon-conducting-back-to-back-exploration-drilling-across-two-guyana-blocks/
thanks,
Celtics.
Biokit also provide Assay Contract Manufacturing.
This could be a manufacturing partner for Avacta's SARS-CoV-2 Lateral Flow Rapid Antigen Test in Europe.
Alistair Smith did allude to manufacturing in Europe recently.
https://www.biokit.com/oem-products-and-services-ivd-industry
https://www.biokit.com/assays?scrollto=c864b0fe8-164e-41d3-9537-cce5ccaf5bbc
Review catalogue button for additional info on the website.
thanks,
Celtics.
Hydrocarbon presence on the Canje block has been confirmed with Bulletwood-1, and is further supported by Tanager-1, which is outward at a similar water depth to Jabillo and Bulletwood.
JHI Associates is fully funded for 4 wells (via Total farm out) and drilling of additional wells.
Note - additional wells and not well.
Effectively, JHI Associates are funded to drill >= 6 wells (one down already) and there are 2 known prospects remaining to be drilled in this current campaign - Jabillo-1 and Sapote-1.
Both prospects are confirmed as having a DHI. Trap integrity appears to be the main risk, not hydrocarbon presence.
Only one successful discovery is required to move the WTE valuation significantly, and with Exxon's exploration success performance in the region to date, I think that the risk to reward ratio is good here.
Other small/mid cap exploration companies that drill are often sufficiently funded for only 2 to 3 wells. JHI is funded for >=6.
thanks,
Celtics.
Notice to Mariners 31 disclosure is likely an error at this stage with Koebi-1 only being recently spud.
It is indicative however that we will soon be spudding Jabillo-1 in my opinion, which I expect to happen in April once Koebi-1 concludes.
https://marad.gov.gy/wp-content/uploads/2021/03/No.-31_2021_EEPGL_Operation.pdf
Thanks,
Celtics.