Member Info for Burble

Great find.

An interesting post 'Lindy noted that they will need a new contract manufacturer for iSCIB1'. Given that we are still waiting for MHRA approval, even if we got that tomorrow, this means that iSCIB1 probably won't start any time soon.

Do we actually know that SCLP are going to the JPM conference? Isn't this conference invitation only.

Looking at the Genmab deal announced on the 25th October 2022 (https://www.lse.co.uk/rns/SCLP/signs-commercial-license-agreement-with-genmab-wsksutknedqtof9.html) we saw the first glymab deal made. With single digit upfront payment, followed by potential milestone payments of up to $208 million for each product developed and commercialised, up to a maximum of $624 million if Genmab develops and commercialises products across all defined modalities.

If you look at the announcement today from C4X discovery (https://www.lse.co.uk/rns/C4XD/astrazeneca-11m-milestone-payment-to-c4xd-irwuew9nnd3ak14.html) where they have just received an £11m milestone payment from AZ for preclinical milestone payment under it's exclusive agreement worth upto £402m. It starts to paint a bit more of a clearer picture for how things may play out here.

C4X announced the original partnership in November 2022 with an up front £2m payment, followed by development milestone payments. So similar timelines to us (obviously v.different drug types and we don't have sight of what Genmab or AZ have deployed to move these products forwards respectively).

It'll be interesting to see when SCLP receiev their first milestone payment.

Happy Christmas Scancellites. Hope you have a fantastic day and here’s to 2024 being another pivotal year!

In addition if you scroll down a few tweets, you see this - https://x.com/DJPinato/status/1730520519936475185?s=20

That's the same disease that Lindy mentioned Modi-1 could go into to test checkpoint inhibitors with...

Agree, especially as Lindy said that many patients cannot go on a full course of CTLA-4 inhibitors because the side effects are too much for patients.

Imagine if iSCIB1+ can mean patients can be given a slightly reduced dose of the CTLA4/anti-PD1 but still get the same effects or better. That would open up more avenues for treatment for patients.

We can live in hope.

Wouldn’t surprise me though if Moderna would be a company to make an early move.

Would really depend on the experiment I guess and what was asked. I also don't know when they submitted to the MHRA and got asked, so it may already be done/in progress. So in short, no.

Violin,

So in response to your 'i simply can't understand why mouse safety studies were not submitted with the original application'.

Something to note, there is a principle within the industry for a thing called the 3Rs with relation to mouse and other animal work. These are replacement, reduction and refinement. It promotes the use of alternative methods where possible, reducing the number of animals used, refining experimental techniques to minimise harm and replacing animals with non-animal models if at all possible.

As such, it wouldn't surprise me if SCLP had done all the pre-clinical work that they believed was necessary to satisfy MHRA requirements to provide approval for iSCIB1+, whilst also adhering to these principals. Therefore they didn't feel it necessary to do further mouse work on iSCIB1+ when they had data to suggest that it was safe/efficacious from other non-animal experiments. Therefore, the submission would have been done without the need for more animal work. After looking at the data submitted by SCLP, the MHRA have requested this animal data.

IMHO, whilst delay is annoying, I have faith it won't delay things too much longer.

Random musing. It wouldn’t surprise me if we get data on this cohort sooner rather than later once the MHRA amendment is granted. I suspect site Principal Investigators may be chomping at the bit to get more of their patients on the study given the earlier results.

I think the limiting factor will be site clinical trials teams being able to process and deploy the amendment. So fingers crossed that they can work efficiently and recruitment can begin as soon as the MHRA green light turns on.

Likewise! That's the christmas money spent.

Cleanerworld the glymabs themselves are a full monoclonal antibody which targets particular sugar motifs. The glycosylation that is described in this video describes sugar molecules which are present on the Fc region of antibodies in abundance. These sugar molecules play crucial roles in the structure and function of monoclonal antibodies and influence various aspects of antibody function including action and half life for example.

Where they talk about duobody technology being compatible with glycosylation in the Fc region, this is because the sugar molecules on the Fc region of antibodies can be engineered as part of a monoclonal antibody development process with the aim of modulating the overall antibody properties. Examples of this are things like enhancing binding affinity of the Fc region to receptors on immune cells, increasing the serum half life (meaning antibodies stay in the blood stream longer), reducing effector functions to improve cytotoxicity, ensuring consistency between batches to improve efficacy and safety, manipulation of properties or addition of non-natural glycan structures.

As such, whilst the glycan antibody licenced from SCLP could be used in a duobody technology platform, it in itself is not the glycosylation that they talk about here.

Not had a chance to listen to the recording fully as I have been at a bio manufacturing conference all week.

Will give it a listen later on the train.

But the cancer type Lindy spoke about that people missed was hepatocellular carcinoma. An aggressive cancer of the liver.

Anyone on here going to the AGM? If so, can you voice note it or record it?

Complete response means that treatments finished as there is no more detectable disease. It does not however mean the patient is cured - hence why normally people say 5 years cancer free for most cancers (10 for some other cancer types) is the point you would be considered cured.

Either way it’s great news for the patient.

Yup! Imagine finding you you have stage 3/4 cancer and then being told ‘you know the trial you signed up to….well because of that you've achieved a complete response’

No wonder recruitment is on track. Wouldnt surprise me if the SCIB1+ trial is recruited in record speed.

Chester - in response to this, no that answer didn't satisfy me. Whilst it explains the discrepancy in data with ORR percentages etc, it doesn't explain why the data presented on each is different. A swimmer chart should be updated as you go along, with the 'lanes' getting longer, but the datapoints that have come before not being updated with each passing week. That's what I think I was getting at - the data seems to have been revised. I'm curious why.

Yes and no - because the target patient population that SCLP therapies treat are not classified as orphan or rare diseases I don't think currently we would. A large push for this change is the fact that many orphan/rare diseases lack any therapeutic development because the current framework means that trials are nigh on impossible, to get enough numbers together to generate meaningful results.

Having said that, where it could help is if SCLP therapies could be demonstrated to target some of those rare diseases where there is no clinical development going on. So for instance, if moditope/immunobody shows effectiveness in their current trials, but these could be pivoted to really rare diseases i could see expedited approval happening.

I think where SCLP can really benefit from this, is the fact that the Immunobody platform is plug and play. So similarly to mRNA vaccines being tweaked for different Covid-19 variants, I could see the DNA plasmid vaccine being approved for one indication, then relatively swiftly being approved for a rare disease indication with minor changes to the DNA backbone and epitopes it targetted without having to go through the full trials process.

Look at earlier versions of immunobody, developed for melanoma, but was used for two paediatric indications (most likely on compassionate use terms). https://www.dailymail.co.uk/health/article-1278836/Holy-Grail-cancer-vaccine-blasts-tumours-weeks-hailed-huge-leap-fighting-disease.html.

Would be keen to hear what others thoughts on this are.

19th September update said ‘Initial data from 11 patients showed an 82% objective response rate (ORR) to treatment, which is better than 70% ORR that the trial was configured to show.’

So where has this 6 patients giving 83% come from? I appreciate that this link is an August presentation, so maybe they had only just got scans by that date from 6 patients, but an explanation would be good to clear up any confusion.

Nope - I've heard nothing back to the two emails I have sent over the past few weeks.

Maybe somebody attending the AGM can raise the lack of response to shareholders via their internet page. I sadly am unable to attend as I'm away at a conference.

I would have to agree with Jamboian.

Providing clarity prevents hearsay. A single line in the results RNS saying 'due to the delay in publishing results, the company believes that it would be appropriate to not reschedule the previously analysts call and instead provide a further opportunity for update at the AGM'. Doesn't have to go into any more detail than that, but at least it stops shareholders, investors and other parties from second guessing themselves or the rumour mill starting up again.