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Verily- google life science subsidiary has moved into nanoparticles for gene therapy. 58m joint venture with verve therapeutics N4p is small fry but the investment funds are out there

Ultimately it would have been better if they did all the studies in one lab- the contract does not specify all the variables that need to be controlled- some they do not know are important. Do they use new or old buffer solutions or what strain of rodent etc Some variables need to be varied so that they can learn about the product- what dose, how frequent the injections The failure of replication was not necessarily incompetence. It would be better if they took a safer approach and replicated in less labs We have strong positive results for pDNA. I haven’t seen the graphical results for mRNA and so am less trusting. We Need it to work for one of them

That wasn’t the problem to be fair UQ/ Aibn will be rigorous with outcome measurement. N4p now won’t them to document the methodology in detail- then they can transfer the tech They are doing a similar task with the manufacture- but the transfer is from lab to industrial plant

If we have have an expanded UQ dataset and the manufacture and Eu- ncl are satisfactory, it may be difficult to imagine at this time.... but we will be in a much better position Of course this depends on the above being OK and confidence is v low atm

The next step is repeating the positive results from the 9 month medimmune collaboration The SP is below the level it was prior to the announcement of those results but replication should be possible- the main result is delay and uncertainty

I think that they have had to balance the pace of nuvec development with standardisation. Going to UoA increased risk by using aother lab but it allowed access to a dna vaccine and would have speeded up development by 6 months of successful. By repeating the same trial in the same lab, but in greater depth they have slowed things down, whilst characterisation and manufacturing catch up

It’s all in Allan hey’s presentation - in particular slides 14 and 15 Manufacture is due to scale up in q3 Euncl due to complete July Repeat UQ trial will take 3-4 months

Btw if they do an identical trial or very similar one in UQ the result is likely to be positive. The magnitude of response is likely to vary due to chance which can be estimated from the confidence intervals. It is possible to be negative even so, though much more likely than when trials are done in a different lab with different, staff, rodents, and other exptal variables

We have now had two positive in vivo trials for pDNA and one for rna, and one negative trial for pdna and two for rna The next one is important in order to reproduce the previous positive results- these showed a dose related response with a specific immune response for both IG2 (antibodies) and interferon (cellular) It will require a wait during which time we hope for updates from Eu-ncl and manufacture

The Eu-ncl characterisation process is independent and should be ongoing in addition to the manufacturing scale up They have put all non essential clinical studies on hold until the UQ testing conditions are fully documented- otherwise they will keep getting inconsistent results

Very annoying as it was avoidable with more thorough planning/processes. The SP has halved in response, instead of doubling AIBN and Medimmune have experience with nanoparticles- maybe the CRO and UoA do not and all the sites are many miles apart, with remote monitoring possible only My main concern is that this is/ can be rectified and we get back on track

Obviously better coordination and communication needed across sites. Very frustrating but it is a relief that they did not find a fundamental problem with nuvec for pDNA. It will mean a delay

They have funding until early 2020. That is when they need positive by

It explains the UoA pDNA results which we expected to replicate. It does not explain the rna results- that needs more info

It would have been much better if they had harmonised their experimental protocols across sites beforehand. This is the the best reason for non replication though.

Some hope- and a sensible way forward

it Was in an rns re the SPV It’s good they are going to the meeting- they could post a photo of PF shaking hands with Per

To a degree we can see what is happening in front of us. Instex is not yet operational and humanitarian transactions will be first in line when it is. There is pressure for this given the recent floods/ relief effort in Iran PF has said instex is not required however and IKAC remain fully committed. There is not much else to say. WSG fits the profile of an SME in possession of technology helpful in the long term development of the internationalised airport city. Will ikac use internal clients if it takes too long?

Yes no scam Big ups and downs with positive then negative results

Mazik I am sorry to hear this- quite a lot of us are suffering at the moment. It’s easy to see why you are fed up- I am hoping this is high volatility rather than a crash We will miss your humorous posts!