Member Info for crumbs

A $2.6 billion IPO.... how can a market get it so wrong?
https://www.fiercebiotech.com/venture-capital/updated-billionaire-soon-shiong-scores-a-record-setting-2-6b-ipo-for-nantkwest

Current mcap $95 million?......

If any one can explain that?

NantKwest

CAR T gets a Scots knockback:

Scotland’s cost-effectiveness watchdog has decided against making Gilead’s CAR-T therapy Yescarta routinely available to patients with two types of lymphoma, but gave a green light to Novartis’ rival Kymriah for a rare form of leukaemia.

The Scottish Medicines Consortium (SMC) approved Kymriah (tisagenlecleucel) for people aged up to 25 with relapsed or refractory acute lymphoblastic lymphoma (ALL), saying that a confidential discount made it “an acceptable use of the limited resources in NHS Scotland.”

Kymriah “offers the possibility of long-term remission and is potentially a life-saving treatment option,” said the SMC in its guidance. The agency is due to deliver a verdict on Kymriah’s other approved indication – diffuse large B-cell non-Hodgkin lymphoma (DLBCL) – in March.

A similar pricing deal secured reimbursement by NHS England for the therapy last September, shortly after Kymriah was approved by the European Commission, and was one of the fastest funding approvals in the NHS’ 70-year history. Novartis charges a list price of £282,000 for a single course of the CAR-T treatment in the UK.

SMC chairman Dr Alan MacDonald said that ALL “is a very rare form of leukaemia which can progress quickly and there are currently very few treatment options for those whose condition has relapsed or not responded.”
https://pharmaphorum.com/news/scotland-says-no-to-yescarta-but-backs-kymriah/

Set for a NICE knockback on lung cancer combo

https://www.cancerresearchuk.org/about-us/cancer-news/news-report/2019-02-12-lung-cancer-treatment-combo-given-initial-nhs-no-in-england

I thought it was to do with tumour responses so if there are 3 patients out of 16 in each cancer target that respond that is enough to expand the trial... or something like that!

I think the market is more focused on funding when it comes to moditope... the modi1 delay is much more understandable than SCIB1 and also moditopes patents have been falling into place as well as modi2 coming onto the scene... so as long as there are no more delays on that platform and I would suggest the recruiting of Adrian means manufacture is very close then apart from the 'how the hell is modi1 trial being funded' question everything moditope is looking very exciting and it would not take much to get that excitement reflected into sp.....

An obvious worry with anything novel that induces such a big immune response is ... will it do something crazy attack self.. well with moditope this does not appear to be the case ...it really is tumour specific:

' However, the antitumor effect is specifically directed against tumor cells as the antitumor effect is reduced in mice implanted with tumor lacking human MHC-II, in the mouse strains HLA-DR4 (survival 20%, p=0.0010), HHDII/DR1 (survival 0%) and HHDII/DP4 (survival 0%) mice. These results suggest that the MPO produced by MDSCs catalyses the build-up of isocyanic acid, which diffuses into the tumor and carbamylates cytoplasmic proteins, which are then degraded and presented by MHC-II. Together these data suggest that MDSCs can mediate carbamylation of proteins within tumor cells, which become targets for cytotoxic CD4 T-cell'

I'm trying to point out that once a therapeutic dose is met... you are not waiting around hoping for something to happen.. it ought to already be happening so long as you have that citrullination recognising CD4s ... you are not blocking a pathway and hoping T cells that once were blocked suddenly see tumour..With moditope it is more a setting off of a chain reaction of an already natural process within most of us whether we have cancer or not... that is the other thing it has been shown to exist in both healthy donors and cancer donors...

If it works moditope will show results very fast once a therapeutic dose is achieved....basically, a CD4 t cell attack stimulated by citrullinated peptides is an innate immune response that most of us already have...moditope overcomes the tumour suppression of that natural process....... least that is my understanding :)

'Citrullination is the post-translational modification of arginine to citrulline mediated by Peptidylarginine deiminases (PADs), which are a family of calcium dependent enzymes found in a variety of tissues. Citrullinated proteins are known to play a significant role in the pathogenesis of autoimmune diseases and are presented in complex with MHC class II. We have previously shown that citrullinated peptides from vimentin and a-enolase are presented on HLA-DR4 in tumor cells and mediate strong anti-tumor responses (Brentville et al., 2016; Cook et al., 2017). Here we show that responses to these peptides are also restricted through HLA-DP4. These responses can be detected within 2 days of vaccination and can mediate rapid regression of tumors within 4 days in mice suggesting evidence of a pre-existing repertoire of T-cells specific for these citrullinated peptides. Evidence of CD4 T-cells specific to citrullinated antigens have been identified in a number of autoimmune disease patients in particular rheumatoid arthritis patients. These patients show an increase in frequency and change in phenotype of citrulline specific CD4 T-cells compared to healthy individuals (James et al., 2014). In this report we also demonstrate that a repertoire of CD4 T-cell responses to citrullinated peptides exists in healthy individuals and that this can be uncovered/enhanced by removal of CD25+ T-cells thus suggesting the existence of a regulatory mechanism keeping these responses in check. The responding populations appear to be oligoclonal and show an increase in effector memory and Temra phenotype. This suggests that a repertoire of CD4 T-cells exists to citrullinated peptides that could be targeted for cancer therapy.'

I think scancell are getting better at explaining moditope at least I think I better understand it now lol... the way of explaining it seems to have evolved with the understanding of it the whole siPTM ... it has come a long way since discovery and scancells understanding of it is much more advanced too... we can but wonder what else they are doing with it behind closed doors... the whole TCR approach coming as a complete surprise .... but you do hear a lot about 'autophagy' these days and recognition of CD4 t cells importance ...which can only be helpful

Sure...I think we are in a kind of limbo at the moment and I have no idea how long it will take before we emerge from it ...we cannot predict FDA on SCIB1 combo we cannot direct CRUK on SCIB2 combo we cannot force BioNtech ( or anyone else on the scene) to sign any cheques... we have no idea what is going on 'behind the scenes'.... well apart from the appointments RNS that I suggest is the one and only clue given... and nothing else :)

That it is becoming recognised that involving CD4 t cells in immunotherapies is needed for a full response does scancell no harm either as we have a way of bringing in killer CD4 T cells so if not even a stand-alone treatment it could well be used in combinations.... really is too early to say until trial data is in... but we have not recruited these new scientists not to have moditope trials that is for sure... how the trials will be funded is the question for investors to me it does not look like it will be funding coming from AIM!... so have to make own conclusions there.

Tumours eradicated in 4 days on one injection in human model mice... it is amazing
Obviously and Lindy herself says as much until trialled in humans there is no way of knowing how effective it will be it could amaze in humans too or it could be underwhelming .... I certainly think it will 'do something' due to it being an understood process that exists already... probably a number of trials would be needed to get to know how best to combine different moditopes... but one thing is certain it is an exciting platform and not only scancell are excited about it

I suppose it is only scancell(that we know of) that have discovered a way to make citrullinated peptides trigger a cancer specific killer CD4 T cell attack... it is interesting how it seems now this a natural process already existing in most of us ,moditope in a way just giving it the kick start to get past tumour supression and once it gets going it does not stop till the job is done...... the difference between life and death in cancer seems to be very tiny

A giant BioNtech cushion at the bottom of the cliff...

Tonight you can throw a few lemmings clinging to a cliff edge into your dreamscape with the odd football flying past :)

Everyone can jump off a cliff like lemmings only for a deal RNS to be announced :)

Remembering from the OO placing RNS:

'The Company is continuing discussions on potential commercial partnership discussions for the Moditope® platform alongside its clinical development plans, with multiple partnering discussions in progress.'

We really only know of BioNtech and yes we have a whiff of Genentech but...'mutiple' suggests more... also modi2 and its many very valuable targets is progressing... the patent covering both modi1 and 2 being in place in Europe and US will only strengthen the deal possibilities... will be interesting to see how this unfolds.

I can only agree it is not a move by a company about to go bust...I think moditope must have attracted serious attention and money is coming towards it one way or another...most obvious being a none IP dilutuve BioNtech TCR licensing deal... however there could be something else...till we know we know nothing :)

It is one them... we may never hear of it again... or we may... I think scancell were correct in putting an RNS out on the day...we have seen the stupid AIM reaction to not winning a prize! It is almost like it is better scancell do not enter such contests at all... you know genentech/BioNtech lost free target trials for their mRNA tech... did it affect them at all? err no not one bit lol... yet scancell somehow have to be punished!...we know we are working very closely with BioNtech the darkhorse is Mellman and Genentech... the future is personalised combination therapies so project blueprint is still something to strive for and it could well be these 4 companies scancell ISA Genentech and BioNtech take the project forwards... we know 2 of the 4 are not skint :)... also CRUK the targets we went for are the ones they are most after treatments for... who knows they might do a SCIB2 deal with scancell on a modi3?.... to go after those targets..... think we need to get this TCR licensing deal out the way first to get to know where next we are heading.