The latest Investing Matters Podcast with Jean Roche, Co-Manager of Schroder UK Mid Cap Investment Trust has just been released. Listen here.
A desalination plant should solve any water supply problems :-)
"Tumour vanishing is what moditope does once that cascade effect kicks in... that is just the science of it"
I believe that Lindy referred to this as the flipping of the immune system. I take this to mean that the immune system no longer regards the tumour as self.
"Berm there is a patient from cohort 1 that has had a positive response which is remarkable given that is from a safety dose"
Also only the 2 vimentin peptides (no enolase peptide).
I suspect that, as the numbers grow, Lindy will be more specific on the 4 different cancers.
At present, the numbers are too small to draw any specific conclusions by cancer type.
7 patients have stable disease as opposed to progressive disease prior to enrolment in the trial.
So, for these 7 patients, it looks like Modi1 is starting to have an effect.
We are all looking for:
a) some of the 7 patients' tumours start to regress
b) more patients start to have stable disease
If this is shown to be happening in the next update, then it is getting more interesting. Perhaps then the market will take notice. I would imagine that there are a few pharmas already taking notice, in particular Biontech and Genentech.
WTP
I take it to mean one patient with partial response from all the cohorts.
https://www.lse.co.uk/rns/SCLP/encouraging-early-efficacy-data-from-modify-trial-nuxyhn2pyg50fgf.html
"Dr David Pinato, Principal Investigator at Imperial College, commented: "Advanced ovarian cancer is an aggressive cancer which is hard to treat. The early efficacy data showing that the Modi-1 vaccine is stabilising this advanced disease is very encouraging"."
The above is the quote that I find most encouraging from the recent RNS.
This is simply because, from all accounts, it is the ovarian cancer cohort that is filling up the fastest. Of course, this is almost certainly due to the fact that CIs are not approved for this cancer.
"Of these patients, one has had a confirmed partial response and seven patients have stable disease, despite having progressive disease prior to enrolment in the study"
If you combine the above statement with David Pinto's statement then it may be deduced that ovarian cancer patients look like they are getting a better treatment with Modi1 than the current standard of care treatment. Of course, the numbers are small so quite reasonably Lindy is still urging caution.
It certainly will be interesting to also see preliminary results of the CI cohorts when these are available. We will then start to see what additional effect, if any, that the CIs will have. Of course, we will also see an updated picture of the monotherapy cohorts.
I agree Wild.
One patient has a good visible response and 7 patients have stable disease. This reinforces the DTH data.
It is a good indication that the T Cells are indeed attacking tumours in some patients.
But I think we should respect the fact that Lindy, at least in public, is treating the results so far with caution.
What she is actually thinking and hoping is that the good start to the trial will continue. A greater percentage of patients reach the stage of stable disease, more patients get a visible response.
I too am on the edge of my seat and the next update cannot come soon enough.
The DTH responses, although very encouraging, do not show vaccine efficacy.
It shows that the CD4 T Cells are being activated and going through clonal expansion at the vaccination site. We also know that some of the CD4 T Cells will differentiate into memory T Cells.
So the DTH responses are not an endpoint but only a necessary step for the next stage which is what happens at the site of the tumour.
We just have to wait for meaningful results of real efficacy. Lindy is quite right in not heralding "it works".
If recruitment for the monotherapy cohorts is still progressing quickly, and the CPI safety cohort is deemed safe, then it should not be too long before we get a further update. Whether the next update will include meaningful efficacy data is still not a given.
“I can’t really believe that result yet; we need to get more.”
A great professional attitude from Lindy
"I.e. Aren't they using/testing SEA-CD40 in context to Avidimab?"
They are indeed WTP.
Maybe Seagen are the US Collaborators with Scancell on the Glymab platform.
Lindy also said that Scancell were talking to 2 companies about Avidimab.
This article may be of interest
https://aacrjournals.org/clincancerres/article/6/4/1347/288151/Delayed-Type-Hypersensitivity-Response-Is-a
"Thirty-two patients who completed a course of immunization with HER-2/neu peptide-based vaccines were analyzed. HER-2/neu peptide-specific DTH responses (n = 93) and peripheral blood T-cell responses (n = 93) were measured 30 days after the final immunization. "
"The findings presented here demonstrate that tumor antigen-specific DTH responses=10 mm2 correlate with measurable in vitroantigen-specific lymphocytic proliferation and are, in this model system, a reflection of systemic immunization."
What is unknown is the size of the DTH responses in the Modi1 trial. The RNS didn't mention this.
Also unknown is how significant it is to have DTH responses this early in the trial, especially 100% of patients having a DTH response.
They are obviously missing Richard Goodfellow
Thanks Burble for this very informative post.
I knew that a mouse day was not the same as a human day, but I didn't realise that typically it is 1 to 40.
So a little over a half of the patients having their cancer stabilised at this stage is really excellent news.
something like this you mean
https://www.ebaumsworld.com/images/the-biggest-gold-nugget-ever-found/81500128/
https://www.trinitydelta.org/research-notes/a-fresh-impetus-in-delivering-immune-oncology-vaccines/
See the paragraph entitled "Combination therapies are seen as the way forward"
"Cancer immunotherapy aims to identify and correct the imbalance so that the cycle becomes self-sustaining again. The difficulty is firstly to ensure a treatment does not overly amplify the immune response, causing an exaggerated autoimmune reaction, but, more challengingly, to ensure tumour cells do not find alternative pathways and so escape. "
Lindy has to provide a balance whereby the immune response is not "overamplified". This involves tipping of the immune response to something that is enough to reduce the tumours but in a controlled manner. I think Wild has mentioned this previously in posts.
I take this to mean that patients will wait a varying length of time before tumours start to reduce.
This can we seen in the famous SCIB1 swim chart
https://www.scancell.co.uk/scib1-iscib1
For some patients 3 doses was enough to become disease-free, whereas for others a lot more than 3 doses were required.
Also, it should be noted that Modi1 is expected to produce a memory effect whereas CIs do not provide any memory effect.
I recall that Lindy was asked the very same question about Modi1 at a presentation some years ago.
"Does the mouse data guarantee success in a clinical trial?" or similar
Her short answer was
"Absolutely not"
I don't think that Lindy will be drawn on speculating on probabilities of success of the Modi1 trial.
However she did say she was very excited :-)
The irony of the TD valuation is that is matters not how many Glymab/Avidimab deals are signed, until the products progress into the clinic the valuation stays the same. That's how I read it anyway.
Ivy
As far as ABs are concerned, the main target was the RDB area of the spike protein.
So no surprise here.
T Cells are another matter which targeted both N and S proteins.
I think we have to wait until the results are published in a scientific journal to get the complete picture.
I was under the impression that this was Lindy's intention.