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The joys of internet communication?

You said:-

'what stands out is that melanoma is increasingly being framed by industry analysts alongside Moderna, Merck and Replimune as one of the leading innovation stories in the sector' -

Given your last post, perhaps you meant to say Scancell rather than melanoma.

CW

I don't quite understand your point. Nothing has changed, melanoma has always been a focus for immunotherapies in development simply because it is the most immunogenic cancer and therefore the most logical place to start for any company. It's why 25 years ago the CPI developers started clinical trials in advanced melanoma before expanding to other cancers and nearly 20 years ago Lindy Durrant developed SCIB1 for melanoma. It always was and sadly always will be a massive market, all we can hope is that with better education, screening and therapies the growth in the market is for curative therapies for early stage melanomas and that advanced unresectable melaoma becomes a thing of the past.

Chelsea,

Scancell's CTA to the MHRA has taken longer than the FDA IND and Phil L'Huillier highlighted this as an area for improvement to help level the playing field for UK biotech. That's it.

Think ee is right and it's probably best to leave it there as frankly I can't believe what I'm reading.

Ee

You are of course perfectly entitled to your opinion but there are plenty of credible explanations and without being privvy to correspondence between the MHRA and Scancell it's impossible to say what the true situation is.

Back in 2023 the MHRA requested additional studies before they would allow Scancell to open the iSCIB1 cohort of the SCOPE study. Scancell carried out those studies and the MHRA subsequently authorised the trial protocol amendment. Since then Scancell have optimised the manufacture of iSCIB1+ with improved thermodynamic stability and have scaled up commercial grade manufacturing in preparation for the phase 3. Part and parcel of the clinical trial application process is full CMC review and for all we know, the MHRA may simply have some questions around this new manufacturing process. Or they simply could have backlogs, staffing issues, be inefficient etc. etc. Who knows?

The point is that Scancell have the most important approval (FDA) and I'm absolutely sure that approval from UK regulators will come in due course. There would be no benefit to anyone in holding up CT approval in the UK whether that's by 'bribery' or 'pressure'. In the meantime, Scancell will simply be getting on with trial preparations.

Ee/chester

The Clinical Trials Unit at the MHRA are responsible for processing and approval of clinical trials applications and I think would argue that they have/are making huge strides to improve turnaround times in order to compete with other regulators. Scancell seem to have been unlucky and tbeir experience this time round hasn't reflected that, but I do remember Lindy Durrant saying how responsive and helpful the MHRA had been when applying for the SCOPE study. Why on earth would anyone take a bribe to hold up Scancell's phase 3 application? Especially as they already have approval in the US and are applying to other jurisdictions. If big pharma were that worried about competition they'd secure the IP for iSCIB1+ via a licensing deal/acquisition rather than resort to bribery to delay a clinical trial in what is sadly a relatively insignificant market for global pharma. So IMO it's probably fair to question the efficiency of staff at the MHRA but there is nothing whatsoever to support questioning their integrity and honesty.

https://pharmaceutical-journal.com/article/news/time-to-approve-uk-clinical-trials-has-more-than-halved-says-mhra

Chester/Vascular

The trial referred to in the link is in the second line setting, for patients who have already been treated and failed on PD-1 therapy whereas Scancell's trial is in the first line setting - ie. patients have had no prior therapy for advanced disease so not a like for like comparison.

Scancell used the Checkmate 067 phase 3 trial as a comparator which is in the same first line setting. I can't find 24 month PFS results for that study but at 18 months the combination of ipi/nivo produced a PFS rate of 46%. Single agent nivolumab, and ipilimumab rates were just 39%, and 14%, respectively. So you can see that the PFS rate of 77% at 20 months produced by the SCOPE study is really quite impressive.

https://www.targetedonc.com/view/combination-nivolumabipilimumab-shows-increased-pfs-compared-with-monotherapy

ASCO starts a week from today and although I can't find any abstracts linked to Scancell amongst the published titles, it would be the logical time to release any positive trial updates. AFAIK Scancell haven't said whether they're attending but it is the biggest and most prominent cancer conference in the world and a chance to meet with potential clinical advisors, investigators, CROs and partners as they have done in previous years. Given the current stage of development, it would be very surprising if they weren't attending.

Wild,

I guess anything is possible. Certainly in the future if they run randomised trials in the adjuvant or neoadjuvant setting with iSCIB1+ in combination then it would have to be with a PD-1 alone as ipi/nivo only has FDA approval in the advanced, inoperable melanoma setting. Would be really interesting at that stage to also include an iSCIB1+ monotherapy arm, ie. to see a 3 arm trial with iSCIB1+ alone v PD-1 alone v combination of the 2. As you know, this earlier setting is where Lindy always thought ImmunoBody would shine brightest.

As far as the current phase 3 goes, I guess it all comes down to funding, whether they partner and if so who with and whether they want to complicate the trial with additional arms if they are certain they'd be applying for approval in combination with the doublet therapy anyway. Worth remembering that the patent they've applied for is for iSCIB1+ in combination with BOTH PD-1 and CTLA4 checkpoints, although it may be that there are other as yet unpublished applications.

Wild,

btw have been meaning to comment re. the FDA Fast Track designation. It's possible that they may well apply for and transition to Breakthrough Designation when full iSCIB1+ phase 2 results are available.

Wild,

Scancell haven't released full trial details but as far as we know it will be a double blinded study with the the treatment arm receiving iSCIB1+ and ipi/nivo and the control arm receving just the ipi/nivo standard of care therapy. The setting will be the same as the phase 2 - inoperable advanced melanoma and assume that it will also be as a first line therapy.

Rc30, very sorry to read your 18.38.

Ray,

Scancell have been using ctDNA liquid biopsy for several years now - see outcome measures for the Modi-1 clinical trial:-

' ctDNA will be measured in blood in patients vaccinated with Modi-1 Moditope either as monotherapy or in combination with checkpoint inhibitors in the target population.'

Following on from Marcus' posts, Scancell have already filed a new patent application for SCIB1/iSCIB1+ in combination with PD-1 Opdivo and CTLA4 Yervoy checkpoint inhibitors:-

'Publication Number WO/2025/061794

Claims

1. A composition for use in a method of treating cancer in a subject, wherein the composition (i) is a vaccine composition comprising one or more nucleic acids encoding a plurality of tumour antigen T cell epitopes, wherein the T cell epitopes comprise GTGRAMLGTHTMEVTVYH (SEQ ID NO: 1), SVYDFFVWL (SEQ ID NO: 2) and WNRQLYPEWTEAQRLD (SEQ ID NO: 3), and wherein the method comprises administering the composition to the subject in combination with

(a) a programmed death-1 (PD-1) inhibitor; and

(b) a cytotoxic T lymphocyte antigen-4 (CTLA-4) inhibitor;

.......................................................................................................

14. The composition for use according to any preceding claim, wherein the PD-1 inhibitor is nivolumab.

15. The composition for use according to any preceding claim, wherein the CTLA-4 inhibitor is ipilimumab'

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2025061794&_cid=P21-MORFPG-08956-2

Headline grabbing news from Wes Streeting today. As you can see from the link below, the subcutaneous injection version of the PD-1 being used in Scancell's trial (Nivolumab/Opdivo) was rolled out by the NHS over a year ago. So perhaps not so much of a massive watershed moment as a natural progression following successful use of the injectable version of Opdivo. Still, it's excellent news for patients.

As far as I can see, Bristol Myers still haven't developed or applied for approval of an injectable version of Yervoy which is the CTLA4 checkpoint being used in combination with Opdivo in Scancell's trial. So patients on Scancell's study will continue to have the combination of CPIs administered via IV infusion with iSCIB1+ being administered by needle-free injection. However, it does show the direction of travel and the the advantage of the method of administration of iSCIB1+ - you would't want to be developing a combination therapy for checkpoint inhibitors that required administration by a more complicated, expensive or inconvenient method such as IV infusion.

On a more general note, imagine having advanced cancer with the pain, trauma and discomfort often exacerbated by the side effects of the treatment being received whether that's chemo or immunotherapy. That's bad enough but then factor in the need to drive over an hour to receive that treatment and then face the drive back again. It's excellent news that those receiving monotherapy PD-1s may now have a much shorter visit to hospital, but let's hope that it won't be long before these injections can be administered by GPs at your local surgery. That would make an even greater difference.

https://www.england.nhs.uk/2025/04/nhs-rolls-out-5-minute-super-jab-for-15-cancers/

Krafty,

Scancell don't necessarily need a partner.

Yes, good news, particularly the updated progression free survival figures. Worth remembering at this point that median survival for the ipi/nivo combination in the checkmate 047 trial was 10.2 months. With PFS of 77% at 20 months, i/scib1+ is still a long way off reaching median survival.

Ee

Only about 1.33 million have vested.

Wild,

Perhaps Sath's share options.

Johnny,

Both sets of share options vested in 3 equal tranches over the 3 years following the grant. The requirement to remain in employment refers to the vesting of the options, not the exercise. In each case only the first two tranches will have vested (see dates below) so unless Scancell have allowed the third tranche to vest as part of some sort of severance package he will currently be holding about 1.33 vested options. Of course he may exercise these before leaving but his contract may allow him to keep any vested options, possibly with a shortened timescale to exercise even after leaving the Company.

'will vest over three years in three equal tranches from 29 August 2024 with no vesting criteria other than to remain in employment'

' will vest over three years in three equal tranches from 19 February 2025 with no vesting criteria other than to remain in employment.'

We'll probably see many different views here in reaction to today's RNS and only time will tell how things will play out but it's worth remembering that sometimes there are no hidden strategies or agendas, sometimes the facts are simply as stated - ie. Sath has decided to move on, Scancell have to replace him and Redmile who obviously will want to protect their investment are offering assistance and putting their man in.

We will never know the circumstances surrounding Sath's decision and it matters not now in any case, but once a CFO has decided to go then the transition needs to take place asap hence the need for this temporary arrangement while they look to recruit a permanent CFO. If this were part of some grand plan and a wider strategy for a NASDAQ listing then it would have been handled much more smoothly with succession planning already in place and a smooth, seamless transition. IMO of course.

David Schilansky has only been in his role at Ariceum for a few months and I can't see that he has announced that he is stepping down, assume that will come today.