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Moonparty,

Have just caught up on your comments re. EVX-01. I haven't seen reports to suggest that Evaxion rejected any patients at 12 weeks - do you have a link? The trial was designed with a planned 1 year interim analysis the results of which were published at ESMO last year. I'm happy to be corrected, but my understanding is that recruitment was stopped after that in order to conserve cash and the 2 year results presented at ESMO this week certainly seem to confirm that is the case. So the trial was scaled right back for strategic reasons rather than rejecting patients.

At the 1 year interim analysis they had screened a total of 21 patients, 17 of these met the recruitment criteria and were enrolled onto the study. One patient withdrew very quickly - I believe due to toxicity of the checkpoint inhibitor and vaccines were manufactured for a total of 16 patients . Evaxion have included all 16 patients in their reporting whether they had progressed or not at 12 weeks.

The number of patients is very small and for that reason alone it's impossible to make too many judgement calls or comparisons but I haven't read or seen anything to suggest that Evaxion have only reported on a 'honed subset of patients'. Also worth noting at this point that when reporting the SCOPE study results Scancell didn't include patients who didn't make the 13 week scan or those cohort 3 patients with the wrong HLA type. Evaxion now have new platforms and a new personalised DNA vax which also uses a PharmaJet device and it will be interesting to see whether they intend to continue with EVX-01 in it's current form or whether they will develop a mark 2 improved version.

For me the most interesting part of the Evaxion story is that they have faced the same battles with valuations and funding despite a licensing agreement and a collaboration with Merck and funding from Merck and the Bill Gates Foundation. Biotech has been tough for everyone over recent years.

Haven't been able to fully keep up with either SCLP board recently so apologies if this has already been posted. ESMO starts tomorrow in Berlin and abstracts have been published. Have copied Scancell's below and hopefully the full poster will be uploaded to Scancell's website in due course:-

'1700eTiP - SCOPE phase II clinical trial program evaluating off-the-shelf DNA plasmid vaccines, SCIB1 and iSCIB1+ administered in combination with checkpoint inhibitors in advanced unresectable melanoma

Presentation Number

1700eTiP

Speakers

Nermeen Varawalla (Oxford, United Kingdom)

Authors

Heather M. Shaw (London, United Kingdom) Philippa G. Corrie (Cambridge, United Kingdom, Cambridgeshire) Poulam Patel (Nottingham, United Kingdom) Miranda Payne (Oxford, United Kingdom) Ioannis Karydis (Southampton, United Kingdom) Kate Young (London, United Kingdom) Clare Barlow (Taunton, United Kingdom) Sarah Danson (Sheffield, United Kingdom, South Yorkshire) Satish Kumar (Swansea, United Kingdom) Rebecca J. Lee (Manchester, United Kingdom) Martin S. Highley (Plymouth, United Kingdom, Devon) Maria Marples (Leeds, United Kingdom, Yorkshire) Ruth E. Board (Preston, United Kingdom, Lancashire) Samantha J. Paston (Oxford, United Kingdom) Joseph Chadwick (Oxford, United Kingdom) Joe Thornton (Oxford, United Kingdom) Robert Miller (Oxford, United Kingdom) Georgia R. Goodhew (Oxford, United Kingdom) Lindy Durrant (Oxford, United Kingdom)

Abstract

Background

SCIB1 and iSCIB1+ are DNA plasmid off-the shelf melanoma vaccines encoding two clusters of CD8 epitopes, TRP-2 and gp100. When administered by needle-free injection these are taken up by Antigen Presenting Cells which directly present the epitopes on MHC molecules to T cells that amplify the anti-tumour immune response, further boosted by dendritic cell cross presentation. Monotherapy SCIB1 induced dose dependent T cell responses in 88% of advanced melanoma patients with minimal side effects (Patel et al, 2018).

In patients with unresectable melanoma, immunotherapy with anti-PD-1 and anti-CTLA-4 checkpoint inhibitors reports an overall response rate (ORR) of 50%, with substantial adverse events (Lebbe et al, 2019). The addition of SCIB1 / iSCIB1+ could overcome the inadequate tumour recognition that causes immunotherapy to fail.

Trial design: The SCOPE phase 2 open label single arm clinical program evaluates within defined cohorts the safety and efficacy of SCIB1 and iSCIB1+ in over 140 patients with unresectable melanoma receiving immunotherapy with ipilimumab and nivolumab at 16 UK trial sites. The primary endpoint is ORR, as measured by RECIST 1.1. Secondary endpoints include duration of response, iRECIST determined ORR, Progression Free Survival and Overall Survival. T cell responses are assessed with a cultured ELISpot assays and adverse events are recorded.

Cont.

'Cohort 1 includes 43 patients with the target HLA haplotype (A2 positive) receiving plus SCIB1 administered intra-muscularly via a needle free injector. In Cohort 2 only,10 such patients, received pembrolizumab.

iSCIB1+ designed to increase eligible HLA haplotypes and avidity is similarly evaluated in Cohort 3, within two sub-groups of 31 and 17, without and with HLA restriction, respectively.

Intra-dermal administration enhances T cell responses in pre-clinical studies and accelerated dosing would prevent disruption of the regimen by checkpoint adverse events. These changes will be evaluated in 40 cohort 4 patients.

Collectively these cohorts will inform optimal product, patient characteristics and dosing regimen for the follow-on randomised clinical trial.

Trial design

The SCOPE phase 2 open label single arm clinical program evaluates within defined cohorts the safety and efficacy of SCIB1 and iSCIB1+ in over 140 patients with unresectable melanoma receiving immunotherapy with ipilimumab and nivolumab at 16 UK trial sites. The primary endpoint is ORR, as measured by RECIST 1.1. Secondary endpoints include duration of response, iRECIST determined ORR, Progression Free Survival and Overall Survival. T cell responses are assessed with a cultured ELISpot assays and adverse events are recorded.

Cohort 1 includes 43 patients with the target HLA haplotype (A2 positive) receiving plus SCIB1 administered intra-muscularly via a needle free injector. In Cohort 2 only,10 such patients, received pembrolizumab.

iSCIB1+ designed to increase eligible HLA haplotypes and avidity is similarly evaluated in Cohort 3, within two sub-groups of 31 and 17, without and with HLA restriction, respectively.

Intra-dermal administration enhances T cell responses in pre-clinical studies and accelerated dosing would prevent disruption of the regimen by checkpoint adverse events. These changes will be evaluated in 40 cohort 4 patients.

Collectively these cohorts will inform optimal product, patient characteristics and dosing regimen for the follow-on randomised clinical trial.

Clinical trial identification

NCT04079166.

Legal entity responsible for the study

Scancell Ltd.

Funding

Scancell Ltd.'

Dracula, there are some major differences including the type of vaccine and trial design. EVX-01 is a personalised vaccine where a tissue biopsy of the patient's tumour is analysed and an AI platform is used to select up to 10 neoantigens that it considers would make the best targets for a vaccine. The vaccine then needs to be manufactured and obviously is tailored only for that patient, so a truly personalised vax. As you know iSCIB1+ is an off the shelf vaccine that can be used on any patient with all the cost, time and scalability benefits that brings.

Both vaccines are being tested in combination with checkpoint inhibitors in advanced, unresectable melanoma. iSCIB1+ is in combination with 2 checkpoint inhibitors from Bristol Myers, the doublet therapy of Opdivo and Yervoy which is the standard of care in this setting. However EVX-01 is in combination only with the PD-1 Keytryuda from Merck who are collaborating on the trial . Scancell also have a very small cohort in combination with Keytruda alone.

The trial design for EVX-01 is very different. Patients commence treatment with Keytruda as a monotherapy to begin with and the vaccine isn't introduced until week 12 . I suspect this may be a case of needs must to allow time for the personalised vaccine manufacture. This is in contrast to Scancell's study where patients are dosed from outset with both the vaccine and the CPIs. Indeed cohort 4 goes a stage further with accelerated priming doses of iSCIB1+ in advance of the CPIs.

Until/unless you run a head to head clinical trial or at least have results of randomised studies for both vaccines in the same setting then it's pretty meaninlgless to make any comparisons in terms of results to date and of course we don't yet know the details of what will be presented at ESMO. Evaxion are also very much testing how effective their AI platform is at selecting the best neoantigens and that's why they place so much emphasis on the fact that 80% of the targets triggered a tumor-specific immune response - apparently superior to other personalised vaccines.

The field is vast and there is plenty of scope (excuse the pun) for both personalised and off the shelf vaccines to co-exist. It's not a case of either/or and the whole field of cancer vaccines needs as many success stories as possible to encourage investors and potential partners.

Ee

The questions may be unnecessary to you but if one person is asking then it's likely others may be too and even if they aren't, does it matter? Perhaps simply don't answer if you feel it's a waste of your time rather than spending that same precious time posting a response that may deter others from asking questions. Your choice, but this is meant to be a place to share information and I have often in the past lazily asked a question to save searching and been grateful for the responses I've always received.

Jackdaw,

Thanks for that. The progress in understanding of how the immune system operates at a molecular level is amazing and this is already bringing real improvements in treatment for all sorts of diseases and hope where previously there was none. Yet there is still so much to learn. If nothing else it shows how incredible and complex the human body is.

Moonparty,

Yes of course. I was responding to ee's post. Assume the focus will be on iSCIB1+ however this is the first major conference Scancell have attended where they'll be wearing two hats - Scancell and Glymab Therapeutics.

AFAIK it's just an eposter :-

'1700eTiP - SCOPE Phase 2 clinical trial program evaluating off-the-shelf DNA plasmid vaccines, SCIB1 and iSCIB1+ administered in combination with checkpoint inhibitors in advanced unresectable melanoma'

Think it has to be held by end of this month and would expect 3 weeks notice so presumably notice of AGM will be issued any day now.

Dracula,

It's disappointing that Genmab haven't yet taken the first mAb into clinical trials but unfortunately it's completely out of Scancell's hands. Genmab had to completely reprioritise their pipeline a while back when BioNTech pulled out of a collaboration with them on one of its mAbs. It suddenly found itself with 3 phase 3 assets to develop. As a result it completely axed some very early stage products to concentrate resources on those phase 3 ones. These things happen and it may explain why it has taken them longer than hoped to take Scancell's first mAb into the clinic but good to see that it wasn't amongst the programmes terminated by Genmab. It does highlight though the ripple effect of completely unrelated events.

Unless it's a one trick pony, at any point in time all biotechs will have products at various stages of development ranging from just a concept through all stages of preclinical and clinical deveopment and sometimes fully approved and marketed. So I don't think it's a case of being far behind, it's simply the stage of development. The original intention with these glycan mAbs was to license them out without any clinical development in order to fund Scancell's cancer vaccines and that's really what they've done with these 2 licensed to Genmab.

Dracula/Violindog

Just wanted to respoond to a couple of posts yesterday regarding Genmab's deal with Merus. The first was the question why they haven't taken a more active role with SCLP. The fact is that Genmab is an antibody developer, that's all they do and unless they have a complete change of strategy and reinvent themselves they're not going to be interested in a cancer vaccine company. It's as simple as that.

That leaves us with the glycan mAbs and of course they already have already shown interest here and backed it with hard cash. We don't know whether they'll be interested or involved in the future developement of other mAbs but this question of the valuation of the Genmab deals keeps raising it's head and now I see a suggestion that they were given mates rates due to an historic connection with Richard Goodfellow. If that were true then the whole board would have to be complicit in backing the deal and of course Vulpes and Redmile have far more to lose than any of us so why would they? They also have a much greater understanding than any of us as to whether the valuation was reasonable.

Merus has a pipeline of antibodies in phase 2 and 3 trials and crucially they are directed a previously proven and validated targets (EGFR, HER2 etc). Scancell licensed mAbs that were at such an early stage that they hadn't yet even been developed into products, let alone entered preclinical or clinical development. Moreover they are against notoriously difficult targets. There are very few companies developing anti glycan mAbs because it's been so problematical in the past. Genmab clearly believe that Scancell are on to something, however the early stage of development and the targets involved are reflected in the heavily back end loaded valuation of the deals as you would expect. So it's not a question of assets being sold of cheaply for mates rates, it's simply a reflection of the nature of the deal.

The bid for Merus is quite a bold move from Genmab, especially as they're apparently part financing it with debt. I guess time will tell whether it was the right one, let's hope so.

Ee

Would need to check but I'm pretty sure PL confirmed that it was at Redmile's request to create liquidity in a couple of it's older funds. The CLNs only impact on headroom if they're converted so if they wanted to create more headroom they'd have to sell some of their existing holding, not request repayment of the CLNs. Also it it were to create headroom then surely that doesn't suggest a deal, it suggests an equity raise.

Chester,

Agree it was a big ask but hard to see what choice either side had. I'm sure Scancell and Redmile would have hoped and expected that 5 years on they'd have been able to convert and sell for a significant profit and wouldn't have needed to even consider repayment but we are where we are. Phil L'Huillier has an impressive track record when it comes to funding and I'm sure has it under control, I just don't necessarily see any connectiion with the early repayment. Having said that, you make a perfectly fair and reasonable point and I hope you're right but equally it could simply be a case of saying no to Redmile who have been very patient and supportive simply wasn't an option.

Chester,

I'm not sure we can read too much into the partial repayment of the CLNs. As you know, the redemption date for these CLNs isn't until 2027 but Redmile can convert at any time. They clearly wanted to realise £1m but these were the interest bearing CLNs which have a conversion price of 13p, meaning that they would have lost money if they had converted and sold immediately. Moreover, the market would have had to absorb around another 7.5m shares which would likely further depress valuations. Rather than having any implications for future funding, perhaps it was simply a sensible and pragmatic decision borne out of a desire to work with and maintain a good relationship with their largest and most important shareholder. Looking on the bright side, at least they'll be accruing less interest:)

Botski,

Re. your earlier post. Huntington's is a dreadful disease for both the patient and their loved ones and how fantastic to see for the first time ever a glimmer of hope with a therapy that actually can slow progression. There's a way to go yet but gene therapy has the potential to transform the treatment landscape for diseases like EB, cystic fibrosis, sickle cell etc. and possibly even offer a cure. At a time when drug development is becoming ever more politicised, it's a great reminder of the real benefit of true science and innovation.

Scancell has updated the Modi trial record on clinicaltrials.gov for the firstt time in nearly 3 years. Changes seem to be mainly around tidying up the language and trial centres and include:-

1) Primary completion date moved from April to July 2026.

2) Study completion date moved from June 2026 to July 2027

3) No. of patients now estimated at 168 (was 144)

4) Reference to avelumab and atezolizumab (PD-L1 checkpoint inhibitors) removed

5) Changes to recruitment status for Brighton, Imperial College London and Cardiff. New trial centres added include Guildford, Mount Vernon, Belfast, Addenbrooke's Cambridge and Torquay - all recruiting. Bristol and Guy's and St. Thomas' removed.

6) Joe Thornton replaces Fayaz Master as Scancell's contact for the study.

Marcus, you're much more up to date than me with Modi related things and you may well spot other changes. Only other thing to add is that given how long it's been since the record has been updated, some of these changes may have happened a while ago. Good to see that primary completion date has only slipped by 3 months though.

https://clinicaltrials.gov/study/NCT05329532?term=scancell&rank=1

Chelsea,

It's standard practice now for companies to do an analyst's presentation when announcing their annual results and it would have been surprising if Scancell had not done one. Timing of the release of those results and the AGM is mostly driven by the timing of auditor's sign off and availability of the board.

WTP,

It's one of the applications related to Moditope and the international patent was filed back in 2021. It entered the national phase of processing back in 2023 and most other patent offices published it back in 2023/24. I don't know why it has only just been published in the US. Interestingly the European application was withdrawn at Scancell's request in March 2025. It may be that they have replaced it with a new application that has yet to be published.

Not sure which Modi this application relates to, cytokeratin isn't one of the targets for Modi-1 so it must be in connection with a future potential Modi. I don't have time to look properly but a quick check didn't reveal the targets for Modi-2 but from memory cytokeratin was one of them. Someone else here or on advfn may know more.

Thanks Burble, good to see first results from cohort 4 are still on track for 2025.

Ruck,

To be fair, I think this is a level playing field and a great initiative to support UK science and technology. These supercomputers have been developed at publicly funded institutions and quite rightly the AI Research Resource (AIRR) initiative is open to all UK researchers whether from academia or industry......but they have to apply!!! The team at Oxford have put a project together and submitted a successful application. That's all there is to it.