Member Info for Vander

The RNS was inaccurate and misleading- as per multiple other WSG RNS over a number of years- this should be addressed formally with both WSG and the nomad

There should also be a formal reply

Interesting article
Medtech scientific company Ltd: are they Wsg plus a local company partnership?
The upgrade of port scanning services has been stymied by government veto of proposed fees increase in aug 21, pending further negotiation- no upgrade work/ even a blueprint had started at this point- wsg have less leverage than MSC Ghana
The funding of installation of new scanners necessitate a fee increase or a Wsg placing? Or maybe this will go into the large WSG archive

They need alternative plasmid to TNF alpha- something which does not kill the host/mouse as well as shrink cancer. Also IV admin means more rigorous safety checks (vs intradermal)

Still very early in the journey though

What’s the latest update on Monrovia?

WSG was one of just 205 organisations nationally to be given the prestigious accolade, which was made at the Prime Minister’s recommendation

Nigel is an affable fellow with full belief in nuvec- he exudes this in his personal communications- he has good ideas and initiatives- the problem is that he is almost a one man band operationally- he does not have the time, inclination or training to follow his good initiatives through meticulously-hence things go wrong and he forgets them as he has moved onto something else- he also needs to diversify beyond nuvec- it could easily fail despite his 100% belief- as happened with the reformulation division-and less experienced investors need to know that

Wsg had planned to take over management of the RVA security staff and improve the working conditions- it would be difficult to be worse

https://www.radiookapi.net/2022/01/10/actualite/societe/tshopo-grogne-la-rva-les-agents-reclament-60-mois-darrieres-de-salaire

We do not have any detail on what positive control was used. Clearly neither it nor nuvec worked in either the initial transfection study or subsequent mouse trial. The Covid plasmid is being delivered to high degree by other vectors in humans- forget small mouse trials. It questions whether nuvec is being developed properly and is a reminder of the failed UoA collaboration in which the preparation of nuvec was poorly documented and communicated- also the aborted EUNCL characterisation which was barely commenced after 9 months of waiting

Keep whipping that dead horse Mayes

There are multiple interested parties willing to see a rise in SP here

I agree- it’s not a trader reaction
Nuvec’s failure to deliver covid plasmid is concerning

All my wsg posts are being deleted

Here is is an article from 2002 in Nature where TNF alpha plasmid dna was delivered by a transferrin-PEI nanoparticle. It’s not new unfortunately. It showed good tumour suppression in mice models of three different cancers but has not been developed further due to off target/ systemic toxicity risk

https://www.nature.com/articles/7700487

Leister- I agree with your comments that a much larger partner is needed- development of a gene therapy vector is highly complex- it needs multiple reiterations of engineering, formulation, added complex components etc. As alluded to in the RNS the vector must be individually and perfectly paired with its delivered gene, in turn specifically developed for route of administration, disease and organ type etc etc
The process is highly integrated requiring multiple disciplines and coordinated in the same company with alot of scientific and financial input. BioNTech and moderna each developed specific LNPs for the individual mRNA molecules for C19. Each consisted of combinations of 4 different lipids but chosen from hundreds of candidate molecules using AI and needed 100s of scientists. Similar for the developers of the LNP for onpattro. They are trying to replicate viral vectors which have the head start of millions of years of evolution

The main point of the TNF work was that nuvec delivered the plasmid when given IV- there is little other detail- unclear how well or how safely
It needs to be compared to an active control
TNF alpha gene delivery will not be a treatment alone- it needs to be somehow activated/ promoted at the disease site- eg by radiation. PEI can be unsafe when given IV due to high positive charge leads to complex formation and agglutination
The key question is whether this data attracts early stage collaboration- it’s unlikely to attract funding in my opinion- but collaborations are needed- it needs scientific development- the (single) catapult scientist is government funded but not the basis for an autonomous company which will grow quickly

Useful article:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792586/

‘Cancer gene therapy using TNF-a has been explored using various approaches to avoid the dose-limiting toxicity. TNFerade, an Ad vector with a radiation-inducible promoter, is the most advanced in clinical development’ -in phase 2/3 human trials

Also TRAIL based therapies have advanced into human trials but have so far disappointed- plasmid DNA delivery by various vectors including PEI is discussed in this article

https://www.nature.com/articles/s41401-019-0287-8

WSG undercut even the local hill billies
Fowler has not mentioned the margin and so unlikely to meet the expected industry standard

Wsg are better at executing one off installations- they may be delayed for a few months as in SE Asia- but eventually happen after approx 9-12 months?
However, the healthy cash balance derives from unused DRC funds
It was a supposed ‘formality’- awaiting parliamentary ratification for implementation by sept 21- unlike all the MOUs, the unilaterally signed contracts (at the request of the AA), the exchanged contracts contracts awaiting board approval, the boots on the ground working for nil for a while contracts, the contracts signed by our partner but not us, and the ones which even when executed do not make a profit

Fowler is less bullish- a bit shaken- a more humble rat

It’s worth considering
1) how confident are we of getting a collaboration with a company delivering TNF alpha for cancer in mouse models- other MTA also possible for vaccine and another gene/plasmid
2) can nuvec deliver dna plasmids when given IV safely and with effectively
3)TNF alpha has been known since the 1970s to shrink tumours- it is toxic when given directly IV- maybe less so when produced locally via dna but off target toxicity possible . TNF alpha inhibitors (ie opposite action) are also considered for cancer. A lot of lab safety work needed prior to human use consideration
4) why did the nuvec not work (so far) as a dna vaccine
Fuller data on the two studies needed to make some judgements on above- Nigel reports adequate funding

The DNA vaccine may not have worked because as a class they are less immunogenic than mRNA although work better given intradermally, where there are more antigen presenting cells to trigger an immune response

A concern however is that the positive control was also negative. This suggests that the mouse trial did not work for technical reasons- Nigel blames the choice of plasmid DNA used- however it is his responsibility to set up the trial adequately especially if key long awaited development outcomes are being tested

This sort of muddle happens when everything is out-sourced without detailed scientific understanding of trial methods/materials. The same thing happened with the Uni of adelaide collaboration where the nuvec formulation method was not properly recorded/documented in UQ and so it could not be made up elsewhere. Poor scientific method, communication and coordination

The TNF alpha trial is positive but more detail is needed- it shows can deliver pDNA- but what value does it add? Can TNF also be delivered by LNPs? Also this is trials on small numbers of rodents in the lab. It will help to get a collaboration with greater buy in on organising all elements of the trial well

MTAs are possible here- but unlikely to have associated funding- still too early stage- more basic science needed inc safety and route of admin
Nuvec needs to have a pathway to human trials and be manufactured at scale imho and MSNs need to be proven as a class
TNF alpha is not an established treatment in oncology- but is a different approach- it’s worth googling- how will you prevent systemic toxicity for example
https://www.frontiersin.org/articles/10.3389/fimmu.2019.01818/full