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[inanaco] 27/2/2023 19:19

actually blood tests are not playing a major part in this ... until the end

Cellular immune response to Modi-1on IFNγ ELISpot assay [ Time Frame: For the duration of the study (12 weeks after the final dose of study treatment

Celluar immune response in the neoadjuvant setting in patients vaccinated with Modi-1 or Modi-1 + Pembrolizumab [ Time Frame: For the duration of the study (6 weeks after resection surgery) ]
Immune cells will be profiled and measured in tumour tissue of patients vaccinated with Modi-1 monotherapy or Modi-1 + Pembrolizumab in patients with SCCHN undergoing planned resection


Other Outcome Measures:
Immune cell profiling in tumour samples [ Time Frame: For the duration of the study (12 weeks after the final dose of study treatment) ]
Immune cells will be profiled from available biopsy tissue

Measurement of circulating tumour deoxyribonucleic acid (ctDNA) [ Time Frame: For the duration of the study (12 weeks after the final dose of study treatment) ]
ctDNA will be measured in blood in patients vaccinated with Modi-1 and Modi-1v either as monotherapy or in combination with checkpoint inhibitors in the target population.

[wigwammer] 27/2/2023 18:57

Yes. And it is predominantly an ovarian trial currently - 78% of patients dosed so far are HGSOC... "23 patients have been vaccinated, 18 with HGSOC, two with TNBC, two with SCCHN and one with RCC, with 55 doses being administered in total."

[inanaco] 27/2/2023 18:26

over all response rate ..... approx 9%

so try and put Scancells data into context ......

[inanaco] 27/2/2023 18:24

now depending on how the trial proceeds ....... in the combo arms

Ovarian with checkpoint as a mono was marginal .... with a PFS of only 2.1 months



Results: 376 pts were enrolled and treated, 285 in cohort A and 91 in cohort B. Median age (range) was 61 (25 to 89) yr, 64.4% had ECOG PS 0, and 75.3% had high grade serous disease. In cohorts A and B, ORR (95% CI) was 8.1% (5.2, 11.9) and 9.9% (4.6, 17.9) in the total population, 6.9% (2.8, 13.8) and 10.2% (3.4, 22.2) in pts with CPS ≥1, and 11.6% (3.9, 25.1) and 18.2% (5.2, 40.3) in pts with CPS ≥10. Median DOR (range) was 8.3 (3.9 to 35.4+) mo in cohort A and 23.6 (3.3+ to 32.8+) mo in cohort B. DCR (95% CI) was 22.1% (17.4, 27.4) and 22.0% (14.0, 31.9). Median PFS was 2.1 mo in both cohorts. In cohorts A and B, median OS was 18.7 mo (17.0, 22.5) and 17.6 mo (13.3, 24.4) in the total population, 20.6 mo (15.2, 23.2) and 20.7 mo (13.6, 27.4) in pts with CPS ≥1, and 21.9 mo (12.9, 26.8) and 24.0 mo (14.5, NR) in pts with CPS ≥10. 73.7% of pts had treatment-related AEs and 20.2% were grades 3-4. There were 2 treatment-related deaths (Stevens-Johnson syndrome and hypoaldosteronism). Immune-mediated AEs occurred in 23.7% of pts. Conclusions: Pembro monotherapy was associated with modest antitumor activity in pts with recurrent AOC. There appeared to be a trend toward increased ORR with higher PD-L1 expression in both cohorts. Responses were durable and typically lasted ≥6 months. Median OS was 18.7 months overall, with a trend toward a longer OS with increasing PD-L1 expression in both cohorts. No new safety signals were identified

how it would behave with Moditope ........ ?

ATB

[inanaco] 27/2/2023 18:11

Wig
because its a phase 1/2 trial the primary measure has to be immune response to the vaccine so that they can best gauge dosage , dose limits and schedule if needed etc

three parts of the vaccine to assess

2 VIM peptides and one enolase

the DTH response won't identify that as one peptide might be sufficient to generate a DTH we don't know

I do not know when the blood tests will kick in

the next update i suspect will be moving the combi arm to full dose however in docs I have read the impact of a Checkpoint is to do with "better expansion" of the CD4 population so a lower dose might actually be showing efficacy because clonal expansion could be higher

lot going on with the trial ...........

but Scancell has the window of whats going on with a Novel Cd4 Killer T cell

the data is of such unbelievable value because nobody else can look at the support that might be needed ....

only Scancell knows the TME with a CD4 killer t cell engaged so in patients that don't respond we can work out why

ATB

[wigwammer] 27/2/2023 17:49

Inan - interesting response from LD, thanks. Note the primary outcome measure for the trial (in addition to AE) is Cellular Immune response using an ELIspot assay, not tumour size... 23 DTH responses = a robust immune response, and the primary goal of the trial is cellular immune response... Perhaps this was chosen as the primary measure because it may be a better proxy for impact on patient survival, the ultimate goal, as opposed to primary tumour size (a secondary measure).

[marcusl2] 27/2/2023 17:11

Valuation, well Trinity are guessing if they make it to market

Moditope peak sales £3.5 billion Royalties 17.5%

Glymabs " £5 billion "

Immunobody " £1.5 "

Avidimab " £8.5 " 8%

[inanaco] 27/2/2023 15:03

CONFIRMATION of my understanding ............. of DTH

copy of email to lindy

Hi Lindy so would you agree with this then

its best described as Covid Arm



a "robust immune response"



Treating COVID arm will not reduce your immune system’s response to the vaccine. Your immune system has already indicated it’s responding robustly.

COVID arm should also not stop you from getting your second shot. Sometimes, your doctor or vaccination provider may recommend alternating arms if you had a strong skin reaction to your first vaccine.

so it appears that people with a robust immune system get covid arm but the majority don't


it would appear Modi1 induces potent response in every patient so far that has taken it highlighted by the DTH response
---------------------------------------------------------------------------------------------------------------------------------------
REPLY

Yes.
lind



Prof Lindy Durrant

CEO

Scancell Ltd

[chilltime] 27/2/2023 14:40

Scancell

The AvidiMab® technology platform is patent-protected and, ultimately, could be applied to enhance the efficacy of potentially any chimeric or humanised mAb.

In addition, the AvidiMab® modifications have also been incorporated into the ImmunoBody® products iSCIB1+ and iSCIB2, and have also been included in the COVIDITY vaccine. In every instance, the modifications have enhanced the preclinical efficacy of these products.

page 21 look at the is iScib v Scib charts, it is a huge difference, that's AvidiMab for you, Scib was good anyway.


Look at the tumour volumes and survival rate.

Lindy said "If you liked Iscib you'll love Iscib" those charts explain why.

[chilltime] 27/2/2023 14:32

The relevant bit

Murine IgG3 glycan-targeting mAb often induces direct cell killing in the absence of immune effector cells or complement via a proinflammatory mechanism resembling oncotic necrosis.

This cancer cell killing is due to non-covalent association between Fc regions of neighboring antibodies, resulting in enhanced avidity.

Human isotypes do not contain the residues underlying this cooperative binding mode; consequently, the direct cell killing of mouse IgG3 mAb is lost upon chimerization or humanization.

they tried it with the glymab sc88 and sc129

when introduced in 88hIgG1, recapitulated the direct cell killing and avidity of 88mIgG3.

The basic point is they found those residues in mice which are potent cancer cell killers, but they are lost in the typical humanisation for Mabs. Avidimab is a way to add them in the process and hence you have a more potent Mab, any Mab.

So what value does a platform have that can potentially enhance any Mab and make it more potent against its target

[inanaco] 27/2/2023 14:25

why would redmile sell for £1 and not wait for Modi2 and the glymabs

when a deal is already in place that could yield $600m ? "one target"

Sorry but no investor going long and in this space would bail at that level £1 its difficult enough as it is to find "golden nuggets" and to have one with such a land grab patent on activating for the first time CD4 Killer T cell and its enormous potential would be like xerox giving away "windows"

if Scancell was a single product ... then yes they could potentially bail

but with so much positive news and scancell clearly demonstrating its ability this is the big One

ATB

[chilltime] 27/2/2023 14:23

I think that's very cheap MT

Redmile and Vulpes have a a successful Avidimab and Modi as multi billion for each.

Take Avidimab

So far indications that it can make any man more potent.

The iscib v scib graph is materially different in favour of iscib.

The Seagen Mab phase II would perform better with Avididmab as in the details. So what value does a platform have that can potentially enhance any Mab.

I was having a read this morning, there are some potent factors in mouse antibodies that get lost in the process to a humanised Mab, that's what Avidimab is all about, the transfer of those murine factors which make Mabs more potent,

So IF Avidimab could make Keytruda more effective, then that may create a new standard of care for Merck on Keytruda, which in revenue terms is massive for them.

Any addition which could extend patents for the majors are of huge importance to them.

Lindy has already said it, iscib should do just that, extend the patent.

[markingtime] 27/2/2023 13:44

If you mean SCLP, I'd suggest it would take a minimum of £1 a share to prise them out. Thats for now.Next year it might be £2.

[torquayfan] 27/2/2023 13:34

Goy - no there isn't !

[octopus100] 27/2/2023 10:53

So Chilltime what do you think SNCL are worth if acquired and what will the majority owners accept.

[chilltime] 27/2/2023 10:25

Interesting times.

Seagen is cancer tumour focused and as we know Avidimab improves what they have as in the trinity note.

On another point as said before such things can't be seen coming. Merck were in talks to acquire Seagen, difference came into play and now it can be seen that Pfizer were also hidden in the background now breaking cover. They were portly doing there DD well before it as known about Merck.

Avidimab if it makes antibodies more potent (it appears it does) then it's an outstanding platform for someone to acquire.

the relevant part re Seagen

SEA-CD40 (Seagen) is in Phase II trials for advanced solid tumours. AvidiMab was used in the Fc region (Exhibit 5) in an IgG1 format, with key residues from murine IgG3 transferred into the human SEA-CD40 IgG1 Fc region. The results for iSEA- CD40 showed higher Fc-Fc self-association, slower off-rate and improved binding to CD40, and better functional affinity than original SEA-CD40. These findings of better performance were also seen in other immune models that rely on clustering and/or increased residence time for activity. Preclinical work continues to highlight the versatility and broad applicability of the AvidiMab platform, with sizable improvements seen across many applications.

[markingtime] 27/2/2023 10:21

Merck were allegedly prepared to pay $200+ for Seagen (which is currently $180, having risen from $120 in December).....other interesting comments here too....https://www.biospace.com/article/merck-seagen-hit-impasse-on-acquisition-deal-due-to-pricing/

[markingtime] 27/2/2023 10:05

Remember that Merck was going to buy Seagen last year but couldn't agree a price.....and has since stated clearly that they now intend to make "small, science-based, acquisitions"..........such as companies with superior science that could damage Keytruda's market???

[marcusl2] 27/2/2023 10:02

Just a reminder, lead antibody in phase II.
Sanofi has agreed to buy British immunotherapy firm Kymab for up to $1.45 billion
Our Non-Executive Chairman Dr Jean-Michel Cosséry was on the board.

[marcusl2] 27/2/2023 09:49

promising early efficacy in a head and neck cancer patient and in other hard-to-treat cancers, said Scancell.

ModiFY is an open-label, multicohort, adaptive basket trial to study the use of Modi-1.

Scancell said that up to 138 cancer patients will be enrolled in the clinical trial of the vaccine candidate. They will be randomly assigned to receive either monotherapy or monotherapy plus standard-of-care checkpoint inhibitor (CPI) therapy.

If the patients are surgical candidates with SCCHN, then the company plans to randomise them to receive either Modi-1 alone or the investigational vaccine with Merck’s pembrolizumab (Keytruda).

[goyathlay] 27/2/2023 09:25

Well TF,

Brook sends down some 65mph dobbler filth and gets a legside strangle, precipitating a collapse.

Is there anything that boy can't do?

[inanaco] 27/2/2023 08:13

so lets look further ......... a universal TCR

once we establish Modi1 TCR's it does not stop at that ...

"universal cancer vaccine"

Here, we identify homocitrullinated peptides from three
different antigens that stimulate homocitrulline-specific
immune responses, restricted through multiple HLA-alleles.
We characterized the response to Vim116-135Hcit peptide and
show stimulation of CD4 responses in Balb/c, HLA-HHDII/DR1
and HLA-DR4 transgenic mice and healthy human donors. We
also show that these epitopes can induce effective tumor therapy
in mouse models. Crucially, cancer patients have a repertoire that
recognizes the Vim116-135Hcit peptide, suggesting that immune
responses to homocitrullinated peptides are not restricted to
autoimmune disease. We suggest that the cross-restriction of
homocitrullinated peptide specific CD4 responses may pave the
way to designing an effective universal anti-tumor vaccine.

Scancell

[marcusl2] 27/2/2023 08:03

Seagen Inc.’s new Chief Executive Officer David Epstein said he’s hunting for deals for emerging oncology drugs while keeping internal focus on the drugmaker’s core technology for attacking tumors.

The company plans to pursue licensing, partnerships or asset acquisitions with biotech startups, Epstein said Tuesday in an interview at the JPMorgan Healthcare Conference in San Francisco. The recent downturn in biotech stocks is pressuring industry

[inanaco] 27/2/2023 08:00

just remember Scancell has produced CD4 TCR clones that have transfected so the principle mechanism works ....

we just need those High Avidity T cells