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Ray,

I was wondering exactly the same thing. We don't know for sure whether patients are being allocated evenly one by one to each arm, but you'd assume so.

Ivy,

Just a quick point about the requirement for a minimum of 15 patients to be negative for antibodies. All that means is that up to 5 patients in each arm can still be recruited even if they have previously been infected with Covid. However, it's still the case that all patients must be completely free of covid (with a negative PCR test to prove it) to be eligible for the trial. Moreover, even if they have a negative PCR test they mustn't have had any known exposure to covid within the previous 2 weeks.

Another peer reviewed research paper featuring Parsortix was published yesterday. This one from the The National Cancer Institute of Milan looks at both tissue and CTC liquid biopsies in triple negative breast cancer patients undergoing neoadjuvant chemotherapy (chemo prior to surgery to remove the tumour).

The study investigates somatic copy number alterations (CNAs)in tumour cells before and after treatment. It's heavy stuff but basically CNAs are changes resulting in a loss or amplification in sections of DNA which frequently occur in cancer (think genetic mutations). I'm not sure we need to know anything more technical than that and if we do then someone else will need to help!

The relevance for holders here is that this is yet another study using Parsortix for molecular analysis to track a patient's cancer through treatment. More importantly, following hot on the heels of the research by University of Southern California Norris Cancer Center (see RNS of 17/1) it is the second study in the space of a couple of weeks looking at using Parsortix as a CTC liquid biopsy in place of a tissue biopsy.

'we hypothesized that liquid could replace tissue biopsies. Indeed, although rather preliminary, our data support the role of CTCs as a tissue-surrogate'

https://www.nature.com/articles/s41598-022-05502-6

BOJO

I like your optimism but the figure of 16 patients is firstly mentioned under the highlights section and you'll notice the words '(including post period)' by the title. Then later under the Covidity section they clearly say 16 patients 'to date'. So either it definitely is up to 22nd Jan or it's very badly drafted. Pretty sure it's the former.

Excellent progress on the R&D side and it's particularly impressive to see the progression in the clinic against the backdrop of a global pandemic. Of course that comes at a price and cash burn now up to just over £27m . On the plus side, the vast majority (nearly £24.5m) of that was spent on R&D. Cash balance at Sep was £29.6m with milestone payments totalling $19m from AZN and Jazz on top of that received post year end. Funding will be required at some point this year, I guess/hope it will take the form of a standard placing rather than debt. Worth noting from the outlook they are also forecasting receipt of further milestone payments this year.

On the product front, the DDR inhibitors sound interesting - looking forward to finding out more.

Konar/Chester,

Think we have to be a bit careful here. Unless I'm mistaken, we were only told that 16 patients had been recruited on 3rd Dec during Lindy Durrant's Proactive One2One presentation. No patients have been recruited since but
we haven't been told that recruitment has been halted/suspended/stopped. All we know is that no patients have been dosed over the past few weeks. We've been told this is largely due to Omicron and of course Christmas fell in the middle of that period. For all we know they have still been actively trying to recruit but have been unable to get any patients through screening - worth noting the inclusion criteria for the trial. It's not just that patients can not have been infected themselves, but also they must have had no known exposure to SARS-CoV-2 virus in the last 14 days. So if they have had any contact with anyone who tested positive for Covid in the last 2 weeks, they have to be excluded.

I agree it's disappointing, but unless there was a conscious decision to officially halt the trial, I'm not sure there was any obligation (moral or regulatory) on Scancell to either inform the market or amend the study status from recruiting. Worth noting that the University of CapeTown Lung Institute still has an appeal for patients to join the trial on its website and the SAHPRA still shows the study as recruiting.

What's matters now is how quickly they can get recruitment back up to speed and how quickly they can move onto dosing with SCOV2 and move towards commencing the UK arm.

ICMRA is a coalition of the heads of the World's medicines regulatory authorities including the FDA and the EMA. They've just published a report looking at Omicron which was summarised in a statement from the EMA today. Worth highlighting some of their findings:-

'With respect to updated vaccine compositions, global regulators encourage the international scientific community and vaccine developers to look at alternative approaches to monovalent vaccines. In the regulators’ view, companies should also explore the feasibility of developing bivalent or multivalent variant vaccines to determine if they offer advantages to monovalent vaccines.'

'Meeting participants also stressed that clinical studies should be undertaken to support the use of a new vaccine. These studies should be designed to demonstrate that the immune response, measured as neutralising antibodies, generated by the updated vaccine is superior to that achieved with current vaccines. The ability of the updated vaccines to cross-neutralise other variants of concern would be an additional feature with respect to the breadth of protection provided by the updated vaccine.'

https://www.ema.europa.eu/en/news/international-regulators-recommendations-covid-19-vaccines-omicron-variant

Dibs,

The article below gives a good summary of the changes being implemented under the Final Rule.

https://www.jdsupra.com/legalnews/de-novo-classification-final-rule-to-3837216/

Should clarify my comment was in respect of the contradictory statements coming from DC and BJ - extraordinary times

AB124

From your 11.47 :- 'neverstatedit'

Sounds like a hashtag that should be trending on twitter ;)

TF,

Fair comment but my point was that the Japanese themselves /the World's top infectious disease experts don't know the reason for Japan's success - they don't know what they've done differently to cause it, so what lessons can you possibly learn and how do you know they're the right ones for a European country?

TF

Japan is an outlier - even their own experts don't understand why they are doing so well. Well worth having a read of the article below. So it's hard to see how Japan can be held up as a fair comparison for any country (even if comparisons are possible). You'd surely have to look to our closer european neighbours.

https://www.npr.org/sections/goatsandsoda/2021/12/20/1065159384/the-riddle-of-japans-dramatic-drop-in-covid-numbers?t=1642186762756

The statement below from the FDA was issued only 3 or 4 weeks ago and makes plenty references to delays caused by Covid. It's well worth a read as I think it helps to explain the huge pressure the CDRH have been working under.

'Since the start of the pandemic, the unprecedented number of EUA and pre-EUA submissions that we received for COVID-19 tests and collection kits significantly impacted our workload, particularly our ability to review IVD submissions that were not related to COVID-19 (non-COVID-19 IVDs). '

https://www.fda.gov/news-events/fda-voices/looking-ahead-2022-fdas-center-devices-and-radiological-health-manages-sustained-increase-workload

Sorry, this is a long post, feel free to ignore!

As highlighted by Ivy earlier, there's certainly a growing recognition of the importance of T cells and the need to look beyond the Spike protein if we're ever to break this cycle of boosting every few months. These are both features of Scancell's vaccine with the potential to set Covidity apart from the crowd.

From outset, Lindy Durrant recognised the advantages of targeting the N protein and the importance of the T cell response to future-proof vaccines against new variants. Scancell already has clinical data showing ImmunoBody generates strong T cell responses and is safe. Moreover, the vaccine has since been further enhanced with Avidimab to produce even more potent responses. I'm not sure how many have fully read the paper published back in June and I think it's worth picking out some extracts:-

'To improve longevity and future protection against variants, we have designed a DNA vaccine encoding both the SARS-CoV-2 spike (S) protein receptor-binding domain (RBD) and its nucleocapsid (N) protein, the latter of which is highly conserved amongst beta coronaviruses. The vaccine elicits strong pro-inflammatory CD4 Th1 and CD8 T-cell responses to both proteins, with these responses being significantly enhanced by fusing the nucleocapsid sequence to a *modified Fc domain.'

*nb. any mention of N fusion modified Fc is Avidimab.

'The N protein plays a vital role in viral RNA replication and the formation of new virions and is therefore highly conserved between coronaviruses . It is present in large quantities and can stimulate a strong immune response. Critically, most survivors of SARS-CoV-2 show evidence of T cell and antibody immunity against the N protein, suggesting that it is a target of the natural immune response. Our vaccine design includes the N protein in order to provide broader immunity'

'We report that the linkage of the N protein to the *modified Fc enhances T cell immunity, and show that the inclusion of this *N-modified Fc fusion alongside the RBD antigen in a bivalent DNA vector stimulates strong cellular and humoral immunity to both antigens'

'High frequency CD8 and Th1 CD4 T cell responses to both RBD and N proteins were stimulated'

'One peptide, conserved between SARS-CoV and SARS-CoV-2 [35], stimulated a esponse in cells from immunised HLA-A2 transgenic mice (N 138–146), thereby highlighting the potential of these T cells to recognise other coronaviruses.'

**In other words, the vaccine recognised and stimulated a response to a peptide from the original 2003 SARS virus that has been conserved in SARS-COV-2.

''we have achieved simultaneous production of strong neutralising antibody titres as well as potent CD8 and CD4 T cell responses to epitopes from both SARS-CoV-2 S and N proteins'

Obviously we need to see these results replicated in the clinic

Ivy,

Thanks for that.

Looking forward to an update on Covidity progress with the interims. Obviously the main focus will be on the number of patients recruited and dosed but just as important will be the manufacture of SCOV-2 as both the UK and SA trials are completely dependent on progress in this area - is manufacture complete and has the vaccine has now been released for use in the clinic?

Similarly with Modi-1 trial, will be good to get an update on trial preparations but also on the manufacture of the enolase peptide .

Krafty,

I agree the timing of JVT's departure is no coincidence but have a feeling that the coincidence is nothing to do with Covid, vaccines or Scancell :)

The Indian DNA vaccine, ZyCov-D a uses the PharmaJet Tropis device and there have been several articles covering the costs of the vaccine and the gun itself which at least give some indication of prices. Zydus were apparently going to charge just under £300 for the gun and less than £1 for the applicator. Obviously a new applicator is required for every jab but apparently the gun has to be replaced after 20,000 shots. Last article I read mentioned that the Indian Government were going to negotiate with PharmaJet to buy supplies directly from them rather than through Zydus. Not sure whether that has happened but if so, I guess they've managed to negotiate a lower price.

Scancell are using both the PharmaJet Tropis device which injects just under the skin and the Stratis deivice which injects into muscle. I assume there's not a great deal of difference in cost or the number of uses.

Another peer-reviewed research paper featuring Parsortix was published yesterday. This one appears to be a collaborative effort from researchers at the University of Southern California (USC), MD Anderson, University Hospital Zurich, Cleveland Breast Cancer Clinic amongst others.

Looking at breast cancer metastases, the researchers were investigating whether RNA sequencing of CTCs could be used in place of tissue biopsies. They found that 'CTCs showed higher expression of immune oncology targets compared with corresponding metastases (tissue biopsies) and PB and there was a high degree of consistency when it came to expression of genes for predictive biomarkers.

Their conclusion:-

'RNA-Seq of Parsortix-enriched CTCs could lead to minimally invasive, real-time diagnostic strategies for precision therapeutic decision making for MBC patients. Our approach could serve as a surrogate liquid biopsy for potentially clinically actionable drug target gene expression and mutations, allowing longitudinal assessment of the evolution of a patient’s cancer.'

Of course 'longitudinal assessment' means monitoring with repeat CTC liquid biopsies. If anyone is interested, it's worth having a read of the comments on the potential of serial CTC harvests to capture changes in the mutation burden as the cancer evolves and responds to treatment.

Small patient numbers and would obviously need repeating in larger numbers but it does show the potential of CTC liquid biopsies to make a real difference to patient's lives. Good stuff.

https://pubmed.ncbi.nlm.nih.gov/35000083/

Dibs,

I believe that with new drug applications the FDA communicates their decision to the applicant before making it public.
They send the decision electronically to the applicant and contact them to confirm that they have received it BEFORE they notify the FDA's press office or update publicly available systems. I assume the same applies to new medical devices. So Angle will have some control over the timing in the sense that they shouldn't have to worry about the decision being announced or leaked by the FDA.

Burble,

I was just about to post a link to Julia Kollewe's original article which was published back in December. I'm pretty sure you were instrumental in initially alerting her to the potential of the Company and she clearly has been impressed enough with the results of her research to nominate Scancell as her 'contender for the headlines in 2022 '. Good stuff and let's hope she's right!

https://www.theguardian.com/business/2021/dec/11/as-covid-mutates-the-vaccine-makers-are-adapting-too