Member Info for extrader

Hi FatherTed,

Thanks for this nuance/link, which prompts a bit of speculation on my part :

Melissa Kapula's description of the challenges (boom boom!) and frustrations in malaria research highlight the value of anything that can contribute to a new approach.

(1) Melissa talks about malaria (a mainly tropical disease, with respiratory side-effects) the time/effort spent in getting a 'standardised' infector...and the problems of finding a 'naive' ie uninfected local supply of research volunteers ie people without NAI Naturally Acquired Immunity;

(2) Andrew talks about typhoid/paratyphoid (now mainly tropical, bacterial) and MrsQuailes, the 'standardised' infector...and mentions that a key issue for regulator was how well the CHIM 'bridged to the population at large'; he mentioned the concern as to how well data /immunogenicity translated from high income to low/middle income countries ;

(3) Chris talks at length about all the precautions and safeguards built into CHIM UK (for the current, global pandemic, with respiratory side-effects) , including use of a GMP GoodManufacturing Process strain of the virus.

The equal airtime given to the 3 makes me wonder if this is part of a wider 'hearts and minds' campaign to encourage a more 'globalist' approach to finding solutions to some of these hitherto intractable diseases.

.."In 2018, there were an estimated 405 000 deaths from malaria globally [ from about 225 million cases, with attendant economic losses] , compared with 416 000 estimated deaths in 2017, and 585 000 in 2010.
Children aged under 5 years are the most vulnerable group affected by malaria. In 2018, they accounted for 67% (272 000) of all malaria deaths worldwide. One in 12 child deaths is attributable to malaria.
The WHO African Region accounted for 94% of all malaria deaths in 2018."

And, circling back, our Dr Chiu is also currently embarking on a Wellcome-sponsored proposed CHIM study in VietNam into dengue, another mosquito-borne disease that ORPH is interested in.

Hmmmmm...

ATB

Hi GGG1111,

.."the relevance to HVIVO is in relation to DIM is this a positive. ?'

Short answer ? I don't know.
Pity there's no edit function here, I meant to add at the end :

.."What is in 'the model', what in 'the protocol' and what in 'the data' would be 'nice to know' info !"

Chiu referred to' IP considerations re the GMP virus', which I'm guessing is CHIMAgents; I'm not clear where /whether data fits in (ie was it just an oversight/not thought relevant in what was a quick 'live chat reply') , which I think is the bit of greatest interest to us from a possible monetisation/wearables perspective.

HTH

Continued/....

The Q and A was mostly on the ethics side

Andrew Pollard was asked about doing CHIMS for 'local disease in a local setting'. He said that for a regulator a key question was how well a CHIM bridged to the population at large. He said that if you wanted to protect children in Asia from paratyphoid, it was better to CHIM in the target population.
OTOH, if you were looking to treat 'naive' children in the tropics for malaria, you would be unlikely to find many 'naive' adults locally for your CHIM study. But using readily available 'naive' volunteers in Northern Europe might introduce other ethical issues- immunogenicity was one he mentioned (data not always transferable from high-income to low/middle income countries).

Chris Chiu was asked about risk mitigation steps, he repeated the 'relatively low risk' and various precautions - minimal dosages; clinician involvement; time invested in making sure that consent was 'informed'; time invested in getting ethics committee on side, public consultations, focus groups etc.

Finally - and perhaps most interesting for ORPH investors - he was asked :
" Will you or hVivo own any intellectual property or data relating to the CHIM C-19 study model and how do you plan to share these assets with other entities ?"
Chris replied initially with :
.." Our aim is to share the model and expertise as widely as possible. we will be publishing the protocol and are very open to collaboration. There are IP considerations relating to the GMP virus, contact me if you wish to discuss."

In follow-up, he expanded on this, I understood him to say that

- UK Vaccine Task Force/HMG 'own the data and the GMP virus' and would share;
- hVivo was willing to share with ' safe' (I took this to mean clinically equipped) partners;
- Wellcome Trust also wanted to share the 'model'.

IMO, E and OE
HTH

Hi all,

Roundtable zoom chat under the auspices of Bill+ Melinda Gates Foundation, keynote speaker yesterday Fauci, today Bill himself.

Presentations and Q + A from Melissa Kapula (Kenya, malaria); Andrew Pollard (Oxford, typhoid, lead on UK CHIM); and Chris Chiu (Imperial, immunologist specialist in respiratory, co-lead on UK CHIM).

From Melissa's presentation , I learned of the back-breaking work in finding an effective treatment for malaria : 434 trials since 2000, including 40 CHIMS.....but only a total of 724 volunteers in 10 countries in the last decade. [So the UK CHIM is actually quite a big deal].The challenge is to research solutions suitable for 'naive' populations (people without 'naturally acquired immunity' NAI) , since the disease is mostly a killer of the young. So a lot of time has to be diverted to understanding the effects of NAI and how to 'unpick' its effects from the research results.

Andrew Pollard spoke about his work on CHIMs for typhoid. His narrative highlighted the importance of a standard strain of 'infector' for benchmarking purposes : a Black American Mrs Quailes has been immortalised by Maryland Uni using 'her' virus as the standard for 1950-1970 and still used for several hundred studies over the last decade.

Chris Chiu opened by putting C-19 in context : 100m cases and 2m deaths attributed; this compares with'flu : 5m cases and 250-500k deaths pa; and RSV : 60m cases and 200k deaths pa. RSV is respiratory syncytial virus, eg bronchitis and pneumonia , bad for kids and the elderly.
Traditional research is 'after the event' : you only see the patient when already unwell; they appear randomly (at different stages of disease progression); there may be random environmental 'confounders' and non-standardised dosages/treatments.
CHIMs offers standardised dosage; reproducible infection rate ; homogeneity of subjects/volunteers; and access to them during all the pre-infection/pre-symptomatic stage; and again afterwards, for long-term follow-up.
Through 'head-to-head' at Phase 2, CHIMs will enable quick elimination of less promising candidate vaccines and significantly de-risk Phase 3 candidates.
Factors that weighed in eventual ethics OK for the UK CHIM included a GMP (good manufacturing practice) grade agent; hVivo track record; containment facility (Royal Free); clinical monitoring; and controlled dose escalation.

Why CHIM now, if vaccines are available ?
- vaccines may confer immunity, but asymptomatic transmission is still a risk to others;
- we need to understand effects/effectiveness of new formulations; different/differently timed doses; durability of protection;
-as 'naive' population shrinks, field testing becomes impractical - and a placebo control almost unethical.

This was all good background for the ensuing Q and A.

Continued/.......

Thanks for this, Ivyspivey, it puts some of the comments made in a slightly different light.

Matt certainly seemed to be more 'aloof' and 'longer term' than the other two, seeing CHIMs as a useful part - but not the whole story -of a bigger picture.

He spoke of seeing them as 'helping us be more prepared for the future, either of this pandemic or the next one'.

ATB

.."The more time that passes the more reassured shareholders should be because the company is duty BLIND to ALTER its shareholders of anything which could adversely affect the company or its shareholders..."

Shome mishtake, Shirley ?

Hi earache,

'It's complicated', as the facebook meme has it.

On the one hand, there are those who say that the adoption of stricter hygiene rules, the disinfectants, the distancing, the (self)isolation has reduced the chance for 'regular' flu to get to us.

On the other, I have young (25-35 year olds) personal acquaintances who describe being curled up for 48 hours in the fetal position with Covid and taking weeks to get back to something approaching 'normal'.

Then there's the 'dry tinder' school of thought , that says that Covid just 'brought forward' a lot of deaths that were going to happen (shortly) anyway.

And then there are the folk who are saying that all your 'flu' candidates are being stored up and this winter the NHS will be overwhelmed with 'flu...some pundits (incl people I've listened to on webinars) saying that we might even have an 'out of phase' flu 'event' in the autumn.....

i suspect that the reality is that not even the experts know for sure; the best thing to do is to err on the side of caution; and review the position in 5 years' time.

Meanwhile, keep behaving 'sensibly', look after your loved ones, take your vitamin D and get lots of exercise.

This too shall pass.

HTH and ATB

.."I also wanted to see the companies that do hold and show that TAG still owns the 72.95%.."
?
TAG owned 72.95% at RTO, after an 18% offload in the Vendor Placing ; it reduced to 50.5% per the 7th July RNS after AZ exercised his call options; and further still after the shareholder re-organisation announced 24 Dec, which saw 1AF2 merge with 'old TAG' and AZ's OrchestraGroup absorbed into 'new TAG' , with 'new TAG' down to 38.9 %.
And 1AF2's claim to a recovery of the 3 x lenders' 18% shareholding kicked further into the long grass.

AIUI.

Hi 99icecream,

With GLEN's fingers in so many pies, it's not inconceivable that they might accept a lower price for Zanaga if there were a trade-off or trade-offs elsewhere.

For instance - speaking purely hypothetically - an 'influential' buyer might be able to encourage a country or two or three to pay off its debt to GLEN or grant it a concession or something else of value to GLEN.

ZIOC is more of a one-trick pony.

All idle musings.

Hi all,

Bullet points from the above, moderated by a bio-ethicist, input from Meta (Leiden Uni, malaria and preparing a C-19 CHIM), Martin (exWHO epidemiologist, spurs in 2003 SARS) and Matt Memoli (US NIH, looking at CHIM for C-19 after a decade spent on 'flu).

(1) aimed at US / Canada audience; the UK experience will hopefully provide a pathway /'cover' for others ( regulatory, political, ethical);

(2) CHIMs aren't a 'magic bullet' but a useful tool :
- they can speed up identification of non-starters; offer greater control of variables; supplement conventional field studies (by targeting under-represented age-groups or ethnicities);
- can test candidate vaccines for effectiveness in reducing transmission (which field studies don't do well) as well as in conferring immunity ;

(3) CHIM limitations :
- they can address 'genetic diversity' but less easily 'immunological diversity' caused by environment, esp. in respiratory viruses : flu vaccine effectiveness is affected by weather, pollution, cigarettes, stress level, exercise, nutrition etc.
- they can help identify eg 6-12month generic 'long tail' issues, but - obviously - not outcomes that may take decades to manifest.

(4) CHIM risks re C-19
- there is no 100% 'rescue remedy' for C-19 and if intervention is needed, it has to be quick, as the young can get it bad;
- to put that in perspective, that's also the case with the flu and RSV (Matt the flu specialist said 'flu was actually higher risk, but manageable because we have 100 years of clinical observation, so fewer 'unknown unknowns');
- for perspective, Martin - a 56 year-old Dutchman , driving average annual mileage - said he was as likely to die in a car accident as from C-19;
- 'left field risk' : although unlikely (based on what is known) , if there WERE to be a fatality in the course of a CHIM, this would set the whole research industry back badly. Maybe obvious, but needed saying.

Other snippets :
- political/public perception is a 'trust' issue : the US Tuskagee syphilis experiments on Black Americans cast a long shadow;
- we don't know, generally speaking, whether immunity from infection or immunity from vaccination is the 'better' in the long term eg in terms of later-life illnesses/medical conditions;
- it makes sense (apart from health issues ) to use the young for C-19 because they appear to be responsible for most asymptomatic transmission;
- because of the lead times, current vaccine manufacturers will have to decide 'in the next month or so' how to tweak to respond to the S African variant;
- CHIMS are a 'powerful but controversial tool' and regulators will probably still prefer conventional Phase 3 'whilst (infectable) people are available...'.

IMO, E&OE

ATB

From the front of the RTO Prospectus :

.."THIS DOCUMENT COMPRISES A PROSPECTUS RELATING TO ABAL GROUP PLC (THE
“COMPANY”) PREPARED IN ACCORDANCE WITH THE PROSPECTUS REGULATION RULES OF
THE FINANCIAL CONDUCT AUTHORITY (THE “FCA”) MADE UNDER SECTION 73A OF FSMA AND
APPROVED BY THE FCA UNDER SECTION 87A OF FSMA. THIS DOCUMENT HAS BEEN
APPROVED BY THE FCA, IN ITS CAPACITY AS COMPETENT AUTHORITY UNDER REGULATION
(EU) 2017/1129 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL OF 14 JUNE 2017 AS
SUPPLEMENTED BY COMMISSION DELEGATED REGULATION (EU) 2019/980, (THE
“PROSPECTUS REGULATION”).
THE FCA ONLY APPROVES THIS DOCUMENT AS MEETING THE
STANDARDS OF COMPLETENESS, COMPREHENSIBILITY AND CONSISTENCY IMPOSED BY
THE PROSPECTUS REGULATION. SUCH APPROVAL SHOULD NOT BE CONSIDERED AS AN
ENDORSEMENT OF THE COMPANY THAT IS THE SUBJECT OF THIS PROSPECTUS OR OF THE
QUALITY OF THE SECURITIES THAT ARE THE SUBJECT OF THIS PROSPECTUS AND
INVESTORS SHOULD MAKE THEIR OWN ASSESSMENT AS TO THE SUITABILITY OF INVESTING
IN THE ORDINARY SHARES OF THE COMPANY.."

HTH

.."Don't forget that ZIOC has tag along rights (which in itelf shows how smart the ZIOC guys are)..."

Smart cookies ! as acknowledged in the last line of my comment ;->

For some reason, I'm getting an image of 2 bald guys arguing over a comb......;->

Apols to the follically-challenged (of which I am one).

ZIOC is much more 'motivated' as seller than GLEN is....and they can bring lots more to the party (cash/connections/ benefits-in-kind eg offtake agreements/marketing/technical support, whatever) than we can.

Plus they're the majority partner.

Our 'half' is 'worth' much less than THEIR half to a buyer, IMO.

I think we'd be lucky to get 25% - 33% of the eventual sale price, maybe we could negotiate some kind of limited life warrant giving us some of the value in the 'tag along' rights....?

IMO

I've just received my notice from Hl/IG (I'm obv. a small fry !).

I'm sure it's just a clerical error, but ZIOC appeared twice on the list....to be sure, to be sure.....

Nice to think that it might be because IG are horrendously exposed to ZIOC and fearful of a massive spike.....

We can but dream.

Hi Fud248,

Yes , pls.
Bearing in mind that the upcoming CHIM tests are paid for by HMG, does it have any rights over the associated resulting data or is this 100% owned by hVivo ?
As an associated follow-on :
In the event of future CHIM and other trials that include data-harvesting, is THIS 100% owned by hVivo or does the paying customer partner that it SHARES the data with have any subsequent right to pass on (or sell) to 3rd parties ?

TIA

Hi all,

The change appears to be only IG at the moment and is linked to the turmoil on stocks like gamestop in the US. IG covers 17,000 stocks or so and has decided (or their fund providers have decided for them) that 1,000 or so are too risky for various reasons.

This link may or may not work, I'll post and then do a workaround if needed
https://www.shiftingshares.com/ig-announces-100-margin-requirements-on-1000-stocks/

I'd hope lse would allow as it's 'public interest'.

There's some unhappiness that some PI's haven't been told about this yet and others heard last Friday.

HTH

Hi all,

I'll be listening in to the schedule-clashing talk on CHIMs this evening from the US 1 Day Sooner crowd, rather than Mello.

Could someone attending Mello report back on any negatives that questioners come up with ? I'm in the bull camp, but would be interested in any real (or imagined) concerns that may be voiced.

TIA

You're welcome.

This was the context : .."I know, for a fact, that they are already talking to very connected people concerning one of the biggest Islamic countries in the world..."

"It's good to talk."

.."Ex, if they don't have much time/patience, I don't see how they are 'connected' people..."

People who have connections tend to be influential and in demand, looking to profit from those connections themselves. So they tend not to suffer fools gladly.
Obviously (?), if they think they'll get something out of it, they'll invest more time. If they don't think something is worth pursuing, they won't pursue.

A bit like Dragon's Den, actually.

HTH