Gordon Stein, CFO of CleanTech Lithium, explains why CTL acquired the 23 Laguna Verde licenses. Watch the video here.
@Wolfiebill, you are indeed asking about the limit of detection, or LOD, and I would point you to research done previously by Ophidian that answers this detail:
===== Posted by Ophidian (9 May 2020 23:53) =====
The Zika Affimer test detects "early" viral loads and from various sources the peak load is an average of 9.9x 10^4 or 99,000 copies per ml this implies that the Affimer detects less than 99,000 as that is pre peak. From the Lancet article (Mar 23, 2020) on Hong Kong patients:
"The median viral load in posterior oropharyngeal saliva or other respiratory specimens at presentation was 5·2 log10 copies per mL (IQR 4·1–7·0). Salivary viral load was highest during the first week after symptom onset and subsequently declined with time (slope -0·15, 95% CI -0·19 to -0·11; R2=0·71)"
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30196-1/fulltext
5.2log10 copies per ml is 158,000 copies per ml. So I would say that at onset of symptoms and probably well before the Affimer concentration on the strip is more than enough to detect the virus based on Zika.
===== END =====
In addition to the above post, Avacta mentioned 11th May they have found Affimers that also bind to the detached spike proteins, so in theory this should lower the LOD even further to below 99,000 copies per ml.
SONA's test is based on a sample via a nasopharyngeal swab, so not exactly the same as Avacta's direct using saliva. This was confirmed by David Regan, SONA's Strategic Advisor.
Captain Stanley - are you invested in here still?
Alistair has already addressed the issue of virus mutation. He says its unlikely to mutate much - which I think he is referring to the spike protein as this is key for the virus particle to bind with the ACE2 human receptor and start the infection process. In any case, it took Avacta 4 weeks to find the best Affimers, so if the spike protein does indeed mutate (and somehow still can bind with ACE2), it won't take long for Alistairs team to find new targeting Affimers.
Ah yes thanks for the reminder Chengdo4! In that case, I think we can be very sure detached proteins can indeed be detected in a LFD, and have a lower LOD as a result.
Also, I've been trying to work out the size of the spike protein vs Affimers. From what I read online, the spike protein is around 20nm in size, whilst the Affimer has a mass of 12-14kDa, which is just over 2nm in size. *IF* more than one affimer can bind to a spike protein, this raises the chance of detached spikes being picked up in a LFT - and lance lowers the LOD further.
@CautiousOptimist - I think it comes down to what viral load is present in people with symptoms. Looking at the FDA template for MOLECULAR manufacturers - which antigen tests are to be compared against - its says in Part J. PERFORMANCE EVALUATION, Section 4:
"At a minimum 30 natural (prospective or retrospective or leftover samples) positive clinical specimens should be collected from patients suspected of SARS-CoV-2 infection by the healthcare provider in the COVID-19 disease endemic region(s)."
So I take this as based on samples of people showing symptoms of COVID19, and not asymptomatic. So again it comes down to viral load. I remember Ophidian sharing (see his post 09 May 2020 23:53) a Lancet report on Hong Kong patients indicated salivary viral load was highest during the first week after symptom onset with median at 5.2log10 copies per ml or 158,000 copies per ml. Ophidian also mentioned the Zika viral load was 99,000 copies per ml, so by reference Avacta's LOD was at least 99,000 copies per ml in that case. So in summary - seems pretty positive!
Thanks to stanman for posting the FDA antigen approval process. It seems the LOD will be a characteristic of the antigen test itself. It appears that the lateral flow device should be tested with lower and lower viral load and the minimum LOD is when 95% of tests (minimum 19 of 20) return a positive result.
===== FDA antigen template section J part 1 =====
Serial dilutions of the characterized SARS-CoV-2 were then tested in [number of replicates] replicates. The lowest concentration at which all [number of replicates] replicates were positive was treated as the tentative LoD for each test. The LoD of each test was then confirmed by testing [number of replicates (at least 20 recommended)] with concentrations at the tentative limit of detection. The final LoD of each test was determined to be the lowest concentration resulting in positive detection of [number of positive replicates (at least 19 out of 20 replicates)]. [Include analysis of LoD results, indicating the final LoD for each test]
===== END =====
Also interesting is Clinical Evaluation (Section J, part 9) on how sensitivity is calculated. Basically the antigen test is compared to a PCR test and minimum 30 natural clinical specimens. This to me sounds like testing those infected and with symptoms, and not asymptomatic patients. To pass here, 80% sensitivity needed so not high a hurdle.
===== FDA antigen template section J part 9 =====
You should confirm the performance of your assay with a series of clinical specimens by testing a minimum of 30 positive specimens and 30 negative specimens in a randomized blinded fashion. We recommend only using a high sensitivity EUA RT-PCR test which uses a chemical lysis step followed by solid phase extraction of nucleic acid (e.g., silica bead extraction) as the comparator method. Specimens may be prospective or retrospectively collected. If you intend to seek a claim for saliva or oral fluid, you should test at least 30 positive specimens with paired PCR results from an NP swab.
...
Tests should demonstrate a minimum sensitivity of = 80% for all sample types submitted.
===== END =====
All these viral load numbers only measure the amount of whole virus particles correct? Note that each virus particle has on average 65 spike proteins, and probably multiples more of detached spikes in the upper respiratory area after infection that can be present in saliva. So while one virus particle has only so much RNA to be detected via PCR, there is a much higher factor when it comes to possible binding targets for Affimers. One would confidently assume then that sensitivity will not be a problem.
https://en.wikipedia.org/wiki/Phases_of_clinical_research
So average 70% chance of success for Phase 1 - "determines whether drug is safe to check for efficacy". So only if the drug is safe or not to use.. not whether it works. The mice drug chart results show you the drug is tolerated very well, at up to 6x dosage.
I suppose with T+3 settlement, you could theoretically sell on Tuesday 26th, and technically have the shares active on 28th to settle. Correct me if wrong.
Also, checking the Molecular Partners share price (SWX: MOLN), the stock has not moved much at all - in fact down since the update.
Molecular Partners provided an update May 7th and shows a lot of promise:
- "These candidates show extremely robust antiviral activity, with several candidates demonstrating complete neutralization with low picomolar potency."
- "the company is preparing for initiation of clinical studies in H2 2020"
https://www.molecularpartners.com/molecular-partners-confirms-ultra-potent-inhibition-of-sars-cov-2-live-virus-by-anti-covid-19-darpin-candidates/
They are slightly ahead of Avacta given they have performed in-vitro testing, as well as starting trials 2H, 2020, but this should give us confidence that our Affimers can do similar. However, it's not clear if Molecular Partners are looking for a large pharmaceutical partner or whether they plan to develop this themselves. So if Avacta can agree a partnership quickly - that would obviously be a positive.
In addition, Avacta have highlighted how their Affimers compare not only to Molecular Partners, but also other competitors to show why it has all the properties of a best-in-class therapeutic protein platform in their Feb 2020 presentation here:
https://avacta.com/wp-content/uploads/2020/02/Avacta-Group-February-2020.pdf (see final slide)
Agreed. Halfway reading through that note, I'm thinking.. why am I not putting all my eggs in this basket!
Myles just released his third update.
https://twitter.com/MylesMcNulty/status/1264244766541307904?s=19
Thanks CO. Just to put things in perspective. The global lateral flow market is currently between US$5-6bn , and around 2bn tests are produced each year. So somehow somewhere there needs a massive scaling up of capacity to meet the most optimistic of expectations here. Possible, but won't happen overnight.
Mologic are a potential manufacturing partner. They have an existing R&D agreement with Avacta, and have mentioned they are developing an at-home antigen test:
https://mologic.co.uk/preliminary-clinical-performance-data-for-professional-use-covid-19-rapid-diagnostic-test/
They also have a new lab coming online soon and can make up to 700k a week. However, they are very focussed on commercialising their antibody test (manufactured by ODX) at cost price.
Would be interested to see your calculations but here's my inputs:
- Probability rapid covid-19 test is successfully released to mass demand: 80%
- Average price per test sold (bearing in mind bulk orders may be heavily discounted): £15
- Cost of manufacturing per test: £2
- Other costs per test e.g. distribution, admin: £2
- Avacta % of profit share with Medusa19: 60%
- Number of months of mass demand: 4
- Average # sold per month of mass demand: 200m
Thanks Kbiztbiz. Yes I thought it was Adeptrix but BAMS testing is not that quick, and Alistair never mentions the BAMS tests as rapid either. Reading the Adeptrix website, it can be a quick as 20 mins, but can also be >1hr+, but it has very high throughput indeed. Anyway, we should find out soon enough.
29. How long does a BAMS™ experiment take?
The immunoaffinity enrichment requires as little as 1 hour but may be extended overnight for capturing low abundance targets. Arraying the beads and eluting compounds from a bead array take less than 1 hour. The above steps may be performed in parallel for multiple samples. A BAMS™ array may be measured in as little as 10 minutes or longer, depending on the number of spots.
https://adeptrix.com/technology
Sorry typo in the title.. Should have said LFT - Lateral Flow Test (or device)