Scancell Share Discussion Threads

[sci102] 30/1/2024 08:32

Between end of Sept and end of Nov 23 additional patients had been recruited, presumably some of them in Sept-Oct so I hope there is something new in the pres.

[miavoce] 30/1/2024 08:25

Yes, hopefully not too long before another update.

[rogerbridge] 30/1/2024 08:23

Can’t wait for the meeting this afternoon.

[sci102] 30/1/2024 08:22

Therefore we should have an update with additional patients

[miavoce] 30/1/2024 08:02

As the period end was 31st Oct the latest SCOPE updates, referred to in the RNS, were post period.

[marcusl2] 30/1/2024 07:48

Looking good.

Safe and well tolerated.

SCOPE trial with 85% ORR reported from the first 13 patients with unresectable melanoma,One patient achieved a complete response

Modi-1 (ModiFY trial)

SIMILAR TO SCIB1
monotherapy in metastatic disease(spread to a different part of your body part than where it started), one patient achieved a partial response and 60% of patients showed stable disease in response to Modi-1 monotherapy.

Modi-1 to be assessed in renal cell carcinoma in combination with double CPI therapy in the ModiFY study pending protocol amendment by the MHRA.

(If that can achieve good results!! PLus eventually permission to treat Ovarian with CPIs)


GlyMab® and AvidiMab® platforms provide potential out licensing opportunities with ACTIVE DISCUSSIONS ongoing with pharmaceutical and biotech companies.

[sci102] 30/1/2024 07:48

They do mention "including post period" in the RNS though

[chillpill] 30/1/2024 07:46

Not surprising.

Results are results- backward looking.

Any new data would come as a separate release.

[sci102] 30/1/2024 07:29

RNS out but no additional update on SCOPE. They should have data on at least 4-5 additional patients and hopefully they'll say more at the presentation.

[plasybryn] 30/1/2024 07:21

Exciting year ahead indeed.

[marcusl2] 29/1/2024 14:25

– lead AvidiMab® modified clinical candidate

iSC2811 – costimulates TILs resulting in anti-tumour immunity
and enhances T cell engraftment for CAR-T development
Ultraspecific SSEA4 mAb

iSC2811 enhances T cell engraftment and prevents exhaustion
Potential for improving CAR-T approaches

(may be licensed on a non-exclusive basis like Avidimab)

[marcusl2] 29/1/2024 11:23

Avidimab could also extend patent lives which could be very valuable.

Covidity;
Professor Lindy Durrant, Chief Executive Officer, Scancell commented, “We are encouraged by these results. The trial validates that AvidiMab®-modified immunotherapies boost immune responses and PharmaJet’s Needle-free Injection Systems are effective in delivering our ImmunoBody®-generated drug candidate. Our plans are to include PharmaJet Needle-free precision delivery systems in future trials with our immuno-oncology projects.”


SCIB1 in advanced melanoma, transitions to the AvidMab enhanced and optimised formulation known as iSCIB1+. This should provide improved potency and efficacy, as well as usefully rejuvenating patent life for ImmunoBody and showcasing AvidiMab’s properties.

The AvidiMab platform can enhance the avidity and potency of any antibody. It is based on specific modifications to the Fc domain of the antibody that result in non-covalent interactions between adjacent Fc regions. The findings arose as part of academic work on glycan antibodies to explore why activity was lost in certain settings. A series of constant region shuffling and subdomain swapping identified the Fc regions involved, with the discovery that introduction of selected residues resulted in retention of the desired effector functions and not only maintained activity but increased it. The initial work was carried out at Nottingham University, with Scancell acquiring the original IP and all rights to the AvidiMab technology in April 2018. Subsequent in-house work has further improved activity, broadened applicability, and created additional IP.

The AvidiMab platform is based on the observation that the mouse IgG3 glycan-targeting mAb often induces direct cell killing in the absence of immune effector cells or complement through a pro-inflammatory mechanism that resembles oncotic necrosis. This was identified as due to a non-covalent association between the Fc regions of neighbouring antibodies, with the inter-molecular cooperativity resulting in enhanced functional affinity and direct tumour cell killing. The effect is caused by key unique sequence residues that are present in the mouse but not seen in the equivalent human antibodies. Essentially AvidiMab can transfer these active residues to any target humanised antibody and so enhance non-covalent interactions between any mAb (or similarly structured) molecules resulting in a material improvement in avidity and potency.

Antibodies are typically described as Y shaped molecules that contain two identical Fab (fragment antigen binding) arms coupled through a hinge to an Fc (fragment crystallisable) domain. The Fab arms provide specificity and mediate target antigen binding, whilst the Fc enables engagement with immune effector functions. Although Fab domains can be therapeutically active, for the majority of effector functions it is Fc that is key. The manner in which Fc interacts can also materially affect an antibody’s therapeutic profile, for instance prolonging half-life and improved binding. Some of the preclinical work on a CD40 antibody enhanced with AvidiMab (named iSEA-CD40) has been presented in two poster sessions (September 2022 and November 2022).

CD40 (cluster of differentiation 40) agonists are a promising area in immuno-oncology as they increase the number and quality of tumour-infiltrating T cells. Theoretically they should be highly effective as a monotherapy or to reverse resistance to checkpoint-blocking antibodies. However, preclinical potency has not yet been replicated in the clinical setting and none of these mAbs have advanced beyond early trial phases. One of the challenges encountered was insufficient immune activation, which resulted in antitumor efficacy only becoming apparent at toxic doses.

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.

[marcusl2] 26/1/2024 08:37

Professor Lindy Durrant, Chief Executive Officer, and Sath Nirmalananthan, Chief Financial Officer, will host a live webcast and Q&A session for analysts and investors at 14:00 GMT. If you would like to join the webcast, please follow this link:

A replay of the webcast will be made available shortly afterwards.

[sci102] 26/1/2024 07:54

We should have more data from SCOPE, end of Nov >20 patients were already recruited and we had data on 13. First evaluation is at 3 months so hopefully we'll have some good news.

[plasybryn] 26/1/2024 07:29

Notice of Interim Results and Presentation Scancell Holdings plc (AIM: SCLP), the developer of novel immunotherapies for the treatment of cancer and infectious disease, will announce its interim results for the six months ended 31 October 2023 on Tuesday 30 January 2024. Professor Lindy Durrant, Chief Executive Officer, and Sath Nirmalananthan, Chief Financial Officer, will host a live webcast and Q&A session for analysts and investors at 14:00 GMT. If you would like to join the webcast, please follow this link: https://www.lsegissuerservices.com/spark/ScancellHoldings/events/f581274b-146c-4a89-af15-05bcae874775 A replay of the webcast will be made available shortly afterwards.

[miavoce] 26/1/2024 07:12

hTTPs://www.investegate.co.uk/announcement/rns/scancell-holdings--sclp/notice-of-interim-results-and-presentation/8007611Results and webcast on Tuesday 30th.

[marcusl2] 25/1/2024 22:54

Carl June ;

Melanoma is a very Hot tumour i.e. infiltrating T Cells can get into the tumour.

In Cold tumours e.g. Pancreatic , Ovarian then one of the key challenges is the immunologically “cold” nature of the tumour microenvironment. They exhibit a low number of infiltrating immune cells, making them less susceptible to immune-mediated destruction.

Modi-1 in Ovarian 44% ORR so if we get permission to use CPI or doublet it could become very exciting for Scancell and patients.

[marcusl2] 25/1/2024 22:34

Re Car-T , I would listen to the main man on the subject.



Drs Carl June and Dan Chen: The Future of CAR-T, Cell Therapy, T-Cell Engagers & Synthetic Immunit


A Moditope TCR would be great to see.
2018, the BioNTech collaboration will initially focus on TCRs specific for the epitopes that underpin Scancell’s lead Moditope candidate, vimentin and enolase.

[rogerbridge] 25/1/2024 16:31

Keep buying!

[marcusl2] 25/1/2024 15:47

From memory Lindy said only 2 or 3 of the 34 neoantigens that Moderna chooses work.

[marcusl2] 25/1/2024 15:46

Burble


MRNA melanoma vaccine publication - June 2023Today 15:37

I finally managed to get my hands on the following publication titled 'mRNA vaccine slows melanoma recurrance'.

This looks at data from the phase IIb KEYNOTE-942 trial which combines moderna's mRNA-4157/V940 with keytruda (pembrolizumab). Briefly this vaccine consists of highly personalised nanoparticle-encapsulated mRNA molecules encoding 34 patient-specific neoantigens. 157 patients, following surgery were randomised 2:1 to receive the vaccine, every 3 weeks for a total of nine shots. At 18 months, the combination cut disease recurrence 44%.

What stood out was the following few quotes.

‘for the first time with a melanoma vaccine, we have randomised data showing a hit of benefit; past trials with different approaches – peptides, dendritic cells, viral vectors – all failed’ said Ryan Sullivan, MD of Mass. Gen. Hospital…’the question now is, are we seeing benefit because this vaccine serves as a nice adjunct to pembrolizumab, providing more T-cell populations with antitumor activity? Or is the key the mRNA platform itself, which seems to be fairly potent delivery system’.

Is Scancell flying beneath the radar? Are people being selective in what they’re quoting? Are people discounting DNA vaccines because mRNA vaccines are in vogue at the moment in this post-covid world?

Then there is a section which goes on to talk about the tumour mutational burden and its relevance to neoantigen vaccines. Where basically they say that TMB may not matter and this ‘could be due to immunodominance’…’whereby out of multiple neoantigens presented, immune responses are skewed towards just a few’….’the problem is there’s no good way to detect immunodominance and it’s still poorly understood’. The article then goes on to quote Jeffrey Weber MD from NY University’s Langone Medical Centre saying ‘bottom line, the number of neoantigens isn’t as important as having the right one’.

This makes me chuckle. Basically, Moderna is throwing the kitchen sink at each patient, taking 34 patient neoantigens, making each patient a bespoke vaccine, and hoping that one of them works and the patient’s immune system generates a potent T-cell response against this. If you choose the wrong ones, the patient gets no or limited benefit. Add to that the additional cost and time taken to produce.

Scancell on the other hand is an off the shelf, with multiple epitopes encoded within the SCIB1 backbone. Yes there is a skill in choosing the right antigens, but once you’ve done that once, you just make it in a large batch and deliver.

If we aren’t fully on everybodies radar….at what point do we start to be.

[marcusl2] 25/1/2024 15:33

Nice find by WeTookPelham


Where are the smart investments under a Starmer government?
From magazine issue:
27 January 2024



A Starmer portfolio

With Starmer in mind, I asked Robin Andrews – the ‘veteran investor’ whose share suggestions served readers well over the past decade – how he might build a buy list for the new political era which, let’s face it (and to quote Philip Larkin), is coming like Christmas.

He picked three sectors bound to be affected by a change of government, starting with housebuilding: if incoming ministers address housing shortages by easing planning rules, then big names such as Persimmon and Barratt will reward the patient investor, as will Forterra in building materials.

Next, defence, and the perpetual search for more bang for Whitehall’s buck. Rolls-Royce and BAE Systems were strong performers last year but they may have further to rise; QinetiQ (the privatised defence research establishment) and Cohort (a smaller collection of defence tech ventures) could also do well.

Finally, pharma, in which any advance that might improve NHS performance or relieve its pressure points must be worth a look. A safety-first approach would involve quoted specialist investment trusts such as Polar Capital Global, Biotech Growth Trust and International Biotechnology Trust – or even safer, a holding in AstraZeneca as a pillar of the sector. But for a little more excitement our man picks three smaller companies in the process of seeking US Federal Drug Administration approval for their products and with reasonable cash runways: Scancell in immunology; Destiny Pharma in infection prevention; and Angle in liquid biopsy technology. Shield Therapeutics, with an iron deficiency drug already FDA-approved, could be a fourth. A spread across those four, plus Cohort, is a bet the veteran investor has already made for himself; but as ever, he urges you to do your own research. And we invite you to send your own Starmer portfolio picks to [e-mail].

[cleanerworldwehope] 24/1/2024 18:21

TF . Why … Woops ! ?

[torquayfan] 24/1/2024 14:48

The heads up from Cleaner again.



A setback for some existing CAR-T projects . . . . BMS and A-Z included.

". . . suggests that even future CAR-T contenders that fits the description will be subject to the same boxed warning. Gracell’s BCMA/CD19 dual-targeting GC012F, which is the centerpiece of AstraZeneca’s $1 billion acquisition of the Chinese biotech, is one such product".

[torquayfan] 24/1/2024 14:00

Yes that was what 6 weeks notice (?) and the next year just an orderly 1 week. For Oct 2023 Interims I expect notice again, but, who gives a sneeze ? Its for the anoraks.

Good to see you posting Inan. I wondered what had energised Ruck over there . . . . .

The Beast is back !