Member Info for RayPointer

Yes C7 and remember that SCIB2 has potential to attack other cancers

"SCIB2 targets the lung cancer antigen NY-ESO-1. It has been developed to the point at which the product is fully defined and ready for further preclinical development as a potential immunotherapy for any tumour that expresses the NY-ESO-1 antigen such as lung, oesophageal, gastric, ovarian and bladder cancers."

http://www.scancell.co.uk/products/product-pipeline

It sounds as though Roche need a lung cancer drug that is more potent than Tecentriq.

Anybody know any contenders?

Don't know if this has been posted in the past but I found this on page 22 of one of the Hardman report re-incarnations.
Adding more epitopes to SCIB1 means that patients do not need to be HLA-A2 positive. This doubles the potential market.

From the Hardman report

SCIB1 PLUS
Scancell is currently investigating SCIB1 PLUS, an improved version of SCIB1. This
newer version is based on a revised ImmunoBody with further epitopes, to allow
treatment of the majority of patients, rather than only those with the HLA-A2
immune sub-type. The use of SCIB1 PLUS would avoid the need for HLA testing and
also double the size of the potential market. It may be particularly relevant for the
treatment of the very large number of patients with resected melanoma ie the
adjuvant indication. In order to pursue SCIB1 PLUS in clinical trials, a small safety
study may be needed prior to efficacy studies.

http://www.hardmanandco.com/docs/default-source/company-docs/scancell-documents/26.09.16-new-frontiers-in-t-cell-activation-and-targeting.pdf

https://en.wikipedia.org/wiki/HLA-A*02

Thanks to you Inan, I now understand the Immunobody processes a lot better and also the associated Immune system processes.

Yes, I get the idea. Sometimes an APC attracts antigen specific T cells and sometimes T cells that are not antigen-specific.
But what it also shows is that there is still so much that scientists don't fully understand about the immune system.
A bit like entanglement theory!

So, once again, the beauty of the science is Lindy's identification of the specific antigen to attack and then finding a way to increase the avidity of the antigen-specific T cells to go after it.

I read somewhere that T cell production in bone marrow creates T cells for just about every antigen it knows about. So, presumably, there are already specific T cells for the target antigen. The problem is that they do not have high avidity. Immunobody provides this avidity.

So

1) SCIB1 working so well on its own
2) Keytruda providing the PD1 blocking
3) Scancell's own combo tests on mice providing superior results to SCIB1 alone or Keytruda alone

You struggle to find reasons why this trial would fail

"Ultra high avidity" T cells, the Jos Buttlers of the T Cell world (apologies to Aussies on the BB)!

1) So presumably the Thymus removes the high avidity T cells since it thinks they can cause more harm than good.

2) The efficiency of Immunobody is provided by
a) the dual presentation
b) electroporalation
So the resultant activity is so intense that it increases the chances of clonal expansion of the CD8 T cells

Is this correct?

The dual presentation of SCIB1 (direct and dual presentation) is the key to success.

Either one of the presentations does not increase the avidity (ability to bind to other cells) of the T cells.
However, together the 2 presentations have a dramatic effect both in the avidity and the numbers of T cells that bind with the APCs. A kind of feeding frenzy.

The high avidity T cells then have a much greater chance of binding with the cancer and killing it.

So, Immunobody works by increasing avidity of existing T cells.

In contrast, Moditope works by activating killer T cells and this activation also causes the cells to rapidly divide and the divided cells inherit the activation, so an army of killer cells is created

So, 2 entirely different methodologies - one based on increasing avidity, the other based on activation and division

Exactly Inan

I can't imagine that it is Scancell's science holding back the IND.

It must be the logistics of having the right people available at the right time and/or Ichor that are delaying matters. As you say, outside Scancell's control and it must really frustrate the BOD.

Take comfort in CH's reply to rHatton's email!

In the meantime, this should keep people busy for a while LOL

https://en.wikipedia.org/wiki/Quantum_entanglement

Agreed leas
The science is on an upward curve and the SP is on a downward curve.
Great for the hoarders like me LOL

Old

Take a bit of time out to try to learn the science.
I promise you that you will not find it boring.
I have started my own learning process recently and I find the immune system fascinating. There are so many different type of cell each performing a particular function or functions.

Try these for starters

https://www.nobelprize.org/educational/medicine/immunity/immune-detail.html

https://www.britannica.com/science/T-cell
(also lots of links to other definitions)

I remember Lindy being very scathing about the withdrawal of 1 patient from the SCIB1 trail because he had a skin rash and itching where SCIB1 was injected by the Ichor device.

Something about "only a man" would withdraw for this reason.

So am I right in saying we have "Skin rash and itching" as the ONLY SCIB1 side effect and, in contrast, death being the worst of the possible Keytruda side effects?

Thanks Wild

From this report:

"At a median follow-up of 15 months, the 1-year recurrence-free survival (RFS) rate was 75.4% (95% CI, 71.3-78.9) with the PD-1 inhibitor versus 61.0% (95% CI, 56.5-65.1) with placebo (HR, 0.57; 98.4% CI, 0.43-0.74; P <.0001)."

If you look at the swimchart for Scancell's SCIB1 Phase 2 trial you will find at 15 months only 2 of the 14 patients had recurrence of the disease and none had died. It should also be noted that disease recurrence only happened after ending SCIB1 dosing.

Also from the report:

"Patient characteristics were well balanced between the 2 arms. In the pembrolizumab arm, 63.0% of patients were male and the median age was 54 years (range 19-88). The breakdown of disease stage at randomization was 15.6% with stage IIIA, 46.1% with stage IIIB, 18.5% with stage IIIC with 1 to 3 positive lymph nodes, and 19.8% with stage IIIC with ≥4 positive lymph nodes."

Lindy set the bar higher in the SCIB1 Phase2 trial, with a median age of 61 (compared to Merck's 54) and 44% of the patients with stage IV (0% in Merck's trial).

You have to take into account that the Scancell trial was with 14 patients whilst Merck's was with 1000. This makes the results of Merck's trial more statistically significant.

ATB

But let's not become News Junkies.

We have Known Knowns - News already issued

Known UnKnowns - News we expect but we don't know when and, for some, we don't know the content

These include:
a) start of each of the 3 trials
b) progress of each of the 3 trials
c) result of the grand challenge
d) possible deal with Biontech

Unknown Unknowns

Left field News - pure speculation

rHatton, Thanks for that.
I just wonder what percentage of INDs have no queries in the 30 day period.
Still, the current situation with the IND (in the final checking stage) is positive.

Interesting TF.

Also further confirmation of the importance of the grand challenge.

We know that in Moditope Lindy has found a way of creating a highly effective army of activated CD4+ T cells.

In Mice trials this army of T Cells has no trouble in infiltrating the Cancer and killing it. The killing army is so powerful that Lindy thinks there is no requirement to add Checkpoint Inhibitors to help with the process.

This is exactly why Ira Mellman is part of the grand challenge team.
He is interested in moditope!!

Thanks for your post Inan. Lindy is also targeting glioblastoma (brain cancer) in the grand Challenge which has a very poor prognosis. https://en.wikipedia.org/wiki/Brain_tumor Prognosis The prognosis of brain cancer depends on the type of cancer diagnosed. Medulloblastoma has a good prognosis with chemotherapy, radiotherapy, and surgical resection while glioblastoma multiforme has a median survival of only 12 months even with aggressive chemoradiotherapy and surgery. Brainstem gliomas have the poorest prognosis of any form of brain cancer, with most patients dying within one year, even with therapy that typically consists of radiation to the tumor along with corticosteroids. However, one type, focal brainstem gliomas in children, seems open to exceptional prognosis and long-term survival has frequently been reported.[43] She has on her team: Professor Michael Platten Professor of Neuroimmunology Country: Germany Organisation: Heidelberg University Discipline: Neuroimmunology https://www.unige.ch/medecine/frontiers-in-biomedicine/prof-michael-platten/

So doesn't this make Advanced Diagnotics/Roche/Scancell a perfect fit. Anyway, off for Pizza now

Surely, the last guy on the team is Woody Allen LOL http://www.cancerresearchuk.org/funding-for-researchers/how-we-deliver-research/grand-challenge-award/shortlistedteamdurrant