The latest Investing Matters Podcast with Jean Roche, Co-Manager of Schroder UK Mid Cap Investment Trust has just been released. Listen here.
I’ve some experience drilling HC wells and interpreting mud gas.
For the uninitiated, drilling mud is a liquid (water or oil based with additives) that circulates down the drill string and up around it in the wellbore, to lubricate and cool the drill bit, prevent blow-outs, and carry rock cuttings up to surface. It also tends to pick up some formation fluids and you’re looking for these in the mud gas. Back at surface, a gas trap in the mud flow line agitates the mud to release some of the suspended gas, which is captured and analysed. You normally get a continuous breakdown of C1 to C5 HC gas components and regular samples in isotubes for later lab analysis, eg every 5-30m, depending on the drilling programme. I presume but don’t know for sure that a continuous log of helium is also possible but they’ll certainly have these spot samples.
For a positive sign of free gas, you’d look for increased Helium as a % of total gas (most of which is just air) in the drilling mud returns. Normally for hydrocarbons, if you get to or above 1 or 2% of total gas it’s very promising. You’d also look for sustained high returns over a long section of the reservoir, rather than anomalous shows in short sections. But no matter how promising, you need other data to confirm a discovery.
The Helium would not be corrupted on its way to the surface, as it is inert, but you never get perfect data. The depth any given sample relates to is estimated from the circulation lag time (ie how long ago was the sample at the drill bit and what depth was it at then). However, the signal does get smeared out, some of the He would escape, and some of it would be recycled back into the hole and come round again, so you have to interpret mud gas in combination with all the other data available.
What you see in the mud gas also depends on a range of other factors, e.g. what mud weight they were drilling with.
If they were drilling significantly over balance (heavy mud relative to formation pressure), it would tend to suppress the formation fluid. If drilling close to formation pressure, you have a better chance of seeing higher helium in the mud gas, but you carry more risk of a pressure kick (unsafe). Such a pressure kick coinciding with increased He would be a very good sign of a gas accumulation, but to minimise the risk of a blow-out, you really don’t want a kick!
They might have had more data to look at from LWD (logging while drilling) tools, but you won’t get pressure/fluid samples to demonstrate a discovery on typical LWD tool strings. If lucky they may have resistivity data, which they can calibrate with salinity from the shallower water samples to estimate the gas saturation in the deeper reservoirs.
In summary, the shows will be real and sound promising, but there isn’t enough data to confirm a discovery. Conversely the fact they are talking about a possible redrill suggests there is not enough data to confirm a failure. More may come out as they work the
The following list of Avacta’s IP patent applications and grants was linked in the LFT Instructions for use:
https://avacta.com/wp-content/uploads/2020/09/IP-page-Avacta-Website-24-September-2020.pdf
Might be old for some here, but I hadn’t seen it before.
Given medical patents last typically 20 years (and in parallel, new drugs being granted approval are granted a period of exclusivity of 5-7 years, at least in the US), it shows the additional IP legs in the cancer therapies side of the business, with the patents dated more recently (2017-2020 for FAPa/PreCision patents licensed to Avacta) than the original Affimer patents, which go back to 2010-13 depending on which territory they were filed in.
Another thought: while the patent for use of the original Affimer platform (Stefan A as a scaffold) may potentially expire in 2030 in Europe, Affimers for specific purposes may be patented separately, such as the PD-L1 inhibitor (licensed to LG Chem with XT serum half-life extension), patented in 2018. As I understand it, this approach gives a longer owned IP life to this and any other highly commercial Affimers which are subsequently patented individually in the same way by Avacta. Prior to 2030, I assume they would get an exclusive run at further specific patents in this IP space, and after 2030, if they develop and patent it first they would maintain IP ownership of Affimers on a function-specific basis.
The modified scaffold (used in therapeutics I think) was also patented a few years later than the initial patent, so again that also has more years to run.
So the IP space is strong, and doesn’t all run out in 2030 as some detractors would have you think.
And if anyone with more knowledge of medical patents has any further insights or corrections on my assumptions above, I’m all eyes! eg there are some further subtleties around the specific types of Affimers or the difference between granted or pending patents.
It sounds like they are saying they don’t have a record of this information (what Ct values are used), so presumably it’s a **** show and there is no consistency between stats from different labs. Quelle surprise.
Why do I feel someone is being led up a garden path with this gnome sequencing?
Great work PL.
I’d predict that the govt fall back on the line of all tests having been rigorously tested at PD. So the concern is that the PD protocols did not follow the manufacturers’ IFU, and the use of spiked, pig mucin and frozen samples did not simulate the live use cases. Such that the Avacta and Mologic tests failed.
So I’d ask:
- Is the government aware that the so-called “rigorous” test validation at Porton Down was not fit for purpose, and actually disadvantaged UK-developed tests (from Avacta and Mologic) that have been independently verified in real-world use cases as two of the top ten antigen LFTs in the world?
- Can the government confirm that the previous “failure” of these tests in the Porton Down process will not cause these tests to be discounted in future, and that the new process will enable them to be validated according to manufacturers’ Instructions For Use, with appropriate clinical human samples (not synthetic positives) that have not been frozen and thawed?
@Ophidian,
Ta. So, date of CE Mark registration with MHRA - when we were told the test could be immediately placed onto the market. Guess we still don’t know exactly when Avacta had the cassettes and other components ready, or when the buffer was ordered.
Conversely, it might just be that since the buffer seems to have a relatively short shelf-life (why only 6 months?), manufacturing it is the very final step (after taking orders) before assembling the kits and shipping them.
Ophidian, agreed - think that explains the final leg of the delay!
But where are you getting this June 7th date from?
Thanks Investor110 - good to see the thing!
I wonder…
Looks like the LFT cassettes could have been manufactured back in May (if 12 month shelf life), then if the quantity shipped is limited by the buffer - it here could be a big stockpile of LFTs made in June and July, ready to go once united with the latest shipment of buffer.
Can anyone confirm this 12 month shelf life for cassettes or am I imagining it? I don’t see that on the package or IFUs anywhere.
Ok, clear from Investor110’s photos on Dropbox - box expiry is driven by the buffer, which seems to have a shelf-life of 6 months at 5-30C. Thanks!
Frustratingly little info, looks like all the LOT and reference numbers on all the boxes and tests photographed have been the same so far.
Someone on Twitter pointed out the expiry date was either 2022-01 or 2022-05.
Look carefully:
It is 2022-01 on the boxes.
2022-05 on the individual tests.
Assuming it’s not a mistake, 2022-01 is perhaps a “sell by” date on the boxes, and 2022-05 on individual tests would be a “use by” date..?
If Hermes - effing Hermes - Hermes, for chrissakes! If them, the driver may just chuck it over your garden fence and you’ll find it a week later covered in cobwebs and somewhat wet. Speaking from anecdotal experience.
Although, whether the shipping is at the courier’s risk or the distributor’s, at least a few failed deliveries would mean more orders from Avacta to replace them! Every little counts. ;)
Strange that they don’t mention POINT Biopharma on that page.
https://www.lse.co.uk/rns/AVCT/license-agreement-with-point-biopharma-inc-4ltd3yd383pyl32.html
…who of course sub-licensed the Precision platform to use with cancer radiopharmaceuticals. Perhaps because it was a commercial deal and may not involve “partnering” in the sense of doing collaborative lab work?
Anyway, that’s another quality therapeutics partnership.
Not irreversibly failed.
This was posted the other day. Last Updated on the 20th:
https://www.gov.uk/government/consultations/private-coronavirus-covid-19-testing-validation/private-covid-19-testing-validation
Says gov moving away from use of PD for private test validation. Also says tests will be validated according to manufacturers’ instructions this time, which is promising. There was some debate as to whether the previous fail at PD would lead to a fail again at the desktop review stage, or just a “gap” to be addressed with further validation.
Good to know, thanks.
Thanks Ophidian for the insights.
Interesting that you say 30C is the uppermost standard storage temperature. That’s the upper limit given on the AffiDx IFUs.
I was thinking wrt supplying hot countries with Affimer-driven diagnostics (eg in Africa via GAH) - for maximum utility in any field setting, you’d really want an upper limit of 40-50C. We know from Avacta’s website that Affimers are stable up to c.80C, so what’s keeping them to 30C on the IFUs? Is that just because it’s the uppermost standard currently in use for stability testing? Or maybe other components that limit temperature exposure?
LDA, re: “Manufacturing will be brought online as demand requires”.
I think we’ll see the biggest steps up once home-use authorisation comes in and Medusa19 do their thing.
A bit of patience needed here.
Great job!
Have you tried squaring them off against this independent evaluation of sensitivity, where tests appear on both?
https://www.medrxiv.org/content/10.1101/2021.05.11.21257016v1.full.pdf
I can’t get my head around how SureScreen was approved so quickly by Porton Down, when they clearly have such appalling sensitivity results! It’s like nobody told us this was a limbo contest, not a high jump.
Possibly. Excerpt below… It’s not entirely clear is it? It could alternatively be read that this previous failure will be captured in the “gap analysis” to be addressed at stage 2. It doesn’t explicitly state that tests which previously failed would be automatically failed again, but that is another possible interpretation. At least step 2 says they follow IFUs, and there’s some complaints process.
Anyway, the UK is just one nation out of many. It’s a nice to have if they fix it this time so AffiDx can pass.
“1. Desktop review
An assessment of the self-declared information from the applicant will be undertaken by a scientific advisor. This will take the form of a half-day desktop review to ensure that the application is complete and meets the minimum standards through a structured gap analysis. This will be supplemented by a check as to whether this test has passed or failed DHSC’s validation process for lateral flow devices or other COVID-19 detection tests for NHS procurement purposes. On successful completion of the review, a bespoke technical validation protocol will be developed to address the identified gaps. The outcome of the desktop review is taken to an expert panel for quality assurance and following this to DHSC’s Technical Validation Group (TVG) for further endorsement prior to going to the Technologies Validation and Assurance Board for final approval. On approval the laboratory undertaking the technical validation will be informed and the bespoke validation protocol shared.
“2. Technical verification
This will involve lab-based testing of the test, to establish its specificity and sensitivity thresholds when used as the manufacturer has indicated it should be used. This will happen over 3 stages. Products completing all 3 stages will have completed validation against the required set of samples in line with the MHRA recommended levels for such a process. This would be the full extent of the proposed assurance and is in line with the MHRA recommended levels. This validation process will ensure that we have a degree of assurance over the performance of a test to be reasonably confident it can be sold.
The details of that test’s validation results will be sent to the TVG and expert panel and then provided to the applicant. Following this the applicant will have the opportunity to lodge an administrative appeal about the outcome. At any time during the process the applicant will be able to make a complaint about service, timescales, and so on. Once this process has been completed the results will be analysed and outcome will be published. This will provide information to consumers to inform their decisions and allow them to check the validation status of tests they may purchase.”
Great efforts all on quizzing your MPs. The DHSC keep falling back on this line about all approved tests being passed through rigorous testing at Porton Down… Such a shame that this otherwise great institution seems either complicit in the corruption, or incompetent and inflexible.
They need to be pressed on why their “rigorous testing” processes involve not following the manufacturers’ instructions for use, in a way that seems to stack the deck against domestic tests which have elsewhere achieved superb validation results. Eg How do they explain their high kit failure rates on the Mologic/ODX Visitect test, which has had decent independent clinical validation?
Don’t forget delivery cost… Which I guess is also £20+VAT.
Pedro, yes there’s no home use authorisation yet, but there’s nothing to stop you from using these tests to inform your own movements especially if seeing elderly family etc. But you wouldn’t be able to report results to add to national statistics, and if you need an official registered test result for anything it wouldn’t be accepted unless administered by a professional.