Member Info for Burble

I read an interesting thing yesterday. At AACR23, Moderna highlighted some of their advances in cancer treatment. In their P2 mRNA-4157-P201/KEYNOTE-942 (https://clinicaltrials.gov/ct2/show/NCT03897881 ) trial which is investigating their patient-specific mRNA-based cancer vaccine in high-risk melanoma.

It was reported that, when combined with an immunotherapy, reduced the risk of disease recurrence or death by 44% in high-risk melanoma patients, compared to immunotherapy alone. https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-NB2023-0028/725913/mRNA-Vaccine-Slows-Melanoma-RecurrencemRNA-Vaccine#:~:text=Findings%20from%20the%20phase%20IIb,therapy%20for%20high%2Drisk%20melanoma

So whilst not a full trial read out from moderna, this gives us an idea of what others are doing in this area. We know that over 85% of patients were still alive 5 years after SCIB1 treatment and that was without an immunotherapy in conjunction with it.

Even more importantly to highlight, the Moderna vaccine is patient specific, with each vaccine dose requiring taking 34 antigen targets unique to a patient, manufacturing them as an mRNA vaccine before delivery. SCIB-1 is off the shelf. SCIB-1+ even more so as the changes Lindy and team have made mean this second version is suitable for a broader range of patients than the original.

I’ll be intrigued to see what results from our SCOPE study look like in comparison. Especially if we have managed to replicate the phase 1 results that we have seen previously.

Possibly.

If the CPI+Modi-1 shows promise, then there's nothing stopping them changing the protocol or adding a separate sub study to include patients who failed front line CPI. Obv. the only downside to that is costs.

Apologies, I hadn't spotted that in my quick scan through. Re-reading it, I wonder whether it comes down to if you're on CPI and it's working, you can join the trial and add Modi-1 to see if it works better.

If you have had a CPI and it's NOT working/not worked, then you cannot join the trial and go back on the CPI in combo with Modi-1.

If you look at the CT page (https://clinicaltrials.gov/ct2/show/NCT05329532)

'Patients scheduled to receive a CPI (e.g., pembrolizumab or nivolumab) together with Modi 1 must have been clinically evaluated, have not received prior CPI therapy, and the CPI must be deemed an appropriate treatment for their disease according to the CPI's SmPC.'

It suggests that patients will only be recruited to the CPI+Modi1 cohort, if they haven't already been on CPI. So recruitment may be slightly slower because the cohort of patients who are eligible for CPI but yet to go on it may be smaller than those who have already started it.

Depends on the reason for being there.

If it’s purely to present interim results, then I would expect the representation to be small or more junior staff. If it’s to present major findings or looking for collaboration partners/funding. Then I would expect seniority to be higher.

These conferences aren’t cheap, so there’s also a balance of how many people to send and also who else may be attending. No point spending money if the conference participants aren’t the calibre of person you want to be interacting with. Smaller companies therefore are v.selective over attending events like this.

There’s also a balance as to who you send and how much they are allowed to talk.

Konar/Bermuda.

Usually title and abstract submitted. If accepted, you turn up with your poster which features both title and abstract. The rest of the poster and any data on that, is not submitted to the organisers beforehand.

What’s interesting with this article is understanding how ahead of the curve we are with modi-1 and modi-2. No personalised biopsies needed. Cheaper to make, off the shelf medicines. Easier to store too for the bonus!

Seems cancer vaccines are back in vogue.

https://www.theguardian.com/society/2023/apr/07/cancer-and-heart-disease-vaccines-ready-by-end-of-the-decade?CMP=Share_iOSApp_Other

The government policy on sustainable air fuels (https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1147350/pathway-to-net-zero-aviation-developing-the-uk-sustainable-aviation-fuel-mandate.pdf) released yesterday mentions gasification plus Fischer-Tropsch technologies producing biofuels to have the greatest potential for net negative emissions given the high concentration of biogenic carbon produced.

I guess this could be of interest to Eqtec as their syngas could be the feedstock for further use in SAF production.

Kash,

Whilst it's difficult when the share price feels stuck in the doldrums. It's important to not consider cancer drug development as a race with only one winner. There are many different types of cancer with distinct underlying biology and clinical characteristics. This means that there is significant room for multiple cancer treatments to coexist in the market.

Whilst there are nearly 300 trials in progress it's important to note that they're not all targetting the same cancer target or the same cancer type and we all know that drug development is highly complex and involves many different stages before regulatory approval is given. Therefore it's not really a single race, but many multiple parallel races. In all of these many of the competitors could fall by the wayside along the way.

It's also important to look at the bigger picture of the benefits scancell has going for it.
- moditope is first-in-class - this is important and has many advantages both to end profit but also regulatory approvals along the way. It also means that for our race, we may be the only people running.
- IP - scancell is very good at patenting things and as stated previously, the moditope platform IP is incredibly broad and therefore incredibly valuable if it is successful. This also would prevent other people joining our race for a while/if at all.
- Target multiple cancer types - both moditope and immunobody can target multiple cancer types. One is more hands on crafting (immunobody) the other targets a common underlying process common to many cancer types (moditope). This means manufacturing and formulation are easier. So now, we have the same horse running in multiple races all on our own.
- Delivery - both are easy to deliver and therefore require less healthcare resources - again reducing costs and leading to better patient outcomes. This also can help too because adoption to become standard of care becomes easier if it helps reduce workload on clinical staff. It's great your horse makes it to the end of the race but if nobody wants it after that because it's difficult to handle/use - it becomes a problem. This shouldn't be the case for moditope or immunobody.
- low toxicity/off-target effects - again provides significant advantage to it being adopted as standard of care both by the clinicians and by the patients receiving it.
- Licensable technologies - SCLP technology allows you to licence technology potentially leading to more collaborations and this also provides bargaining chips when negotiating.

Yes I don't think our share price reflects how good our potential is. But I also suspect this boils down to two things - one is PR (we've all said this could be better), the other is stage. Moditope especially is still unknown, as the picture becomes clearer we should see the value start to increase - possibly exponentially.

Bermuda.

You share similar thoughts to me. IMHO we should focus on the information that SCLP have given us directly as investors and leave the speculation out of it.

Others may disagree, but that’s my position and I’ll stick to it.

Interesting to note - https://www.gov.uk/government/news/chancellor-unveils-a-budget-for-growth.

'The Medicines and Healthcare products Regulatory Agency (MHRA) will receive £10 million extra funding over two years to maximise its use of Brexit freedoms and accelerate patient access to treatments. This will allow, from 2024, the MHRA to introduce new, swift approvals systems, speeding up access to treatments already approved by trusted international partners and ground-breaking technologies such as cancer vaccines and AI therapeutics for mental health.'

The fact it's specifically noted cancer vaccines - suggests that we may continue to have favourable tail winds

The thing is with these events (be it AACR, or PEGS or any other of these huge conferences), is that it's the back room conversations which are why people go. They're not there to listen to academics or industry witter on ad nauseam, so much of this type of conference is about having the appetite whetted through rapid fire, short presentations and breakout sessions with posters, then most people are there for the networking events on the side and after the conference each day.

Botski, that's the session length. There are 20 presentations given across this time.

The full text of the Clinical Trial and Late-Breaking Abstracts will be posted to the AACR Online Itinerary Planner and the Meeting App no earlier than 12:00 p.m. U.S. ET on Friday, April 14, 2023, except those abstracts that are selected for inclusion in the official AACR press program. Abstracts that are featured in the official AACR press program will be made publicly available at the date and time of presentation, either at the meeting or an official AACR press conference.

In previous years, abstracts accepted for presentation at the AACR Annual Meeting were published in an online-only Proceedings supplement to the AACR journal Cancer Research after the conclusion of the meeting. Beginning in 2023, the Proceedings supplement will be published prior to the meeting in two parts. Part 1 of the online Proceedings (regular abstracts) will be published on Friday, March 31, and Part 2 (clinical trials and late-breaking abstracts) will be published on Friday, April 14.

Revised Proceedings supplements containing the full text of embargoed abstracts as well as any late change will be published in Cancer Research approximately one month after the meeting.

Thanks for that. It's also worth focussing on the fact that this is being presented by LD herself.

If you look at AIM RNS’s there seems a coordinated statement from many - same wording for all those not affected.

When you look down the list, there are a few which have exposure - some minor, others major. So I suspect it’s a requirement of the stock exchange to notify shareholders accordingly.

I feel for those other companies and shareholders who are exposed, sometimes by a considerable amount!

‘TillyMint was 1st cohort is Modi-1 LOW DOSE , correct? If so that's even more impressive IMO.’

Correction. She was the first patient in cohort 2

Yup it surprised me too - I blame my racing insomniac brain this morning for asking me that question. But I'm kind of glad I did because it further puts people's minds at ease that we're still early days. Especially if you then compare that to other immunotherapies which take a few months before they start showing promise. Next Modi-1 update should be interesting.

A further observation from me. I was thinking at what we already know about Modi-1 data in the public sphere.

AGM presentation - https://www.scancell.co.uk/Data/Sites/1/media/docspres/agm-presentationnovember-2022_final.pdf

Look at page 11 - there is a bulletpoint which states 'tumour regression seen within 4 days of Modi-1 vaccination'

If you think about mice models, it's generally suggested that 9 mouse days is the equivalent to a year as a human (https://www.sciencedirect.com/science/article/abs/pii/S0024320515300527?via%3Dihub). Or 1 mouse day is approximately 40 human days. I wonder whether many people following this share have conflated the two and thought that we would be seeing regression within 4 days. Yes in mouse models, but this is humans we are now talking about.

So based on the Scancell data if this translated directly into humans, we should be looking at starting to see regression of tumours from about 160 days i.e. nearly 6 (5.2) months into the trial.

Look at Figure 2Aii on the Modi-1 paper (https://jitc.bmj.com/content/jitc/8/1/e000560.full.pdf). The circles indicate the day of immunisation and X indicates day of tumour analysis. For some of these mice, you see an immediate regression of tumour bulk. But for some (blue, pink, orange) you see stabilisation of their tumour without regression over about a 10 day period (i.e. approximately a year in human time) before which animals were sacrificed and tumours analysed. In the control, you see continued tumour growth. This is then shown again in the 2Aiii figure waterfall plot. We don't know how long this stabilisation continues because the mice are sacrified early, but if that continued for longer, then you could be looking at a patient who has exhausted all current treatments, being given at least a year if not more to their lifespan even if Modi-1 doesn't remove tumour bulk.

In the rechallenge work that was done also in this paper, this was performed in mice at 58 days. So in humans that would suggest a rechallenge equivalent in humans of 6 years after the initial dosing of Modi-1.

Taking those together, what we saw in the mouse model data is being reflected in what we are seeing in the clinic.