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I can't remember I'm afraid and the actual recording has not been posted online.
To add to that, in the notes I took, I have written 'Genmab for ADC to treat pancreatic cancer.' Unsure whether anybody else can flesh this out further.
Something that stood out to me was how much Lindy stressed using the mAbs for ADCs. We know from things hitting up across the sector that ADCs are coming into vogue, especially if you can get ‘exquisite specificity’ to target your drug to your cancer cells.
I wonder whether LD was dropping hints about what indications people are exploring these for. Lots happening in this space,
https://www.biospace.com/article/biopharma-industry-continues-to-bet-big-on-antibody-drug-conjugates/
Interesting also Sath said something during his financial presentation saying something along the lines of 'depending on finances, we may look to take TC134 into the clinic ourselves'. This refers to the highly selective antibody which SCLP has reformatted into a T cell redirecting antibody.
Written questions submitted
Are you still looking to raise further cash next year on the back of trial results?
Sath: Cash raise highlights that the cash runway runs through to 2025 and we anticipate that this may be boosted with further deals/milestone payments which would be non-dilutive. Worth noting that we have a strong cash position but we have value creation in mind.
How likely are Scancell to receive income from avidimab and glymab in the near term?
With the pre-clinical deals, the up front payment from GenMab of £6m is what we would anticipate for deals done. There is a good chance we will get one or two of these deals over the next 12 months, some of those evaluating the glymabs are ongoing, some are new.
Do you plan to run the iSCIB1+ Phase 2/3 trial in US and UK.
Yes this will an IND under the FDA and we would look to run it in the UK and US. We would like to do Europe but unlike in the US/UK, in europe you need to pay for checkpoint inhibitors in Europe. So that would be about £100k per person on the trial. In the UK/US means because CPI is standard of care, you do not need to pay for this. Though this may chance and if we can run trials in europe we would look to do so.
Franc Gregori - Trinity Delta
With SCIB1 - would it be sensible to accept partnering with the data you have now or would you get better value at first phase 2 data on study?
LD: We would get better value if we wait. We anticipate to get the best value would be after the phase 2 adaptive design - would probably be when we get a good deal. Though obviously it all depends on the deal.
Edward ??? (didn't catch surname) - Singer Capital Markets.
E? - A broad question on doublet therapy combination in modi-1. BMS released positive data this week in colorectal cancer. Is this a potential patient cohort to expand into?
LD: This is a subset of patients which has a high mutation frequency. The data is stunning. They almost don’t need a vaccine in there. In theory - anything where there is a double checkpoint approved we could put [modi-1] vaccine alongside. As we prove double checkpoints are the way forward with this vaccine. It's also important to note that many of these CPIs are coming off patent and biosimilars are coming on the market. As such, good data with double checkpoints will mean a good market out there for modi-1.
E? - Have you seen interest from 3rd parties with SCIB1
LD: Yes there has been interest, most pharma - want to see 43 patients at least.
We anticipate going into randomised phase 2 before partnering. You have to take it further than ADCs which can do deals pre-clinically or after Phase 1. We will see interest further if data is stunning. but we need to complete one of these studies first.
James Osbourne - Stifel
JO: in relation to ISCIB1 MHRA approval, will you use the same sites for recruitmetn of patients. How do you expect recruitment to progress with both arms going forward?
LD: Initial idea is patients who are screening failures due to HLA type will go into the iSCIB1+ cohort. We will continue to recruit patients to SCIB1 until full.
Same centres will be used, two new centres have being brought online and a further two new centres to start in April. The quickness to recruit to the iSCIB1+ cohort will be down to screen failures for the SCIB1 arm. 2 out of 3 of patients fail and will go to iSCIB1+ arm of the trial.
JO: WRT the glymab platform, you talk about 5 potential partners which has increased from 3. Have you seen a step change in frequence of these conversations?
LD: Genmab gave people a vote of confidence. However, the ones who are currently evaluating the platform are fighting for exclusivity. This does pose a bit of an issue for us. Each partner needs to evaluate with their own drug checking whether their antibody and drug work together.
JO: SCOPE data is highly encouraging are you beginning to see a shift in sentiment towards cancer vaccines?
Do you see it being a patient numbers game.
LD: Yes there is definitely interest in cancer vaccines, it would be very nice if this starts looking positive in some of the randomised studies. The Moderna data will be important in spurring interest in cancer vaccines - though that will be another 3-4 years before we get that data. The sooner the better.
I've also then written '5 ADCs being developed towards a single antibody target - but unsure what that specifically relates to, whether that's a following question or not. Am on the train atm so have lousy signal.
Q&A - Mike Mitchell - Panmore Gordon
MM: Regarding teh Phase 2/3 adapted trial, the assumption is this would be an iSCIB1+ trial. What is the relative risk with the iSCIB1+ cohort and could this fall back and be SCIB1 only.
LD: Yes you’re right, we anticipate it will be iSCIB1+ but clearly it’s down to what happens in the clinic. In bigger cohort of patients, it’s a much more marketable drug. If for some reason it was too potent, or doesn’t work in as many patients as we want, we can go with SCIB1
LD also mentioned that a new patent has recently been filed with SCIB1 in combo with double checkpoint.
MM: In trial design, are these decisions which need to be made now? Is a partner required before you begin?
LD: The benefit of the adaptive approach is that we can plan now and start the phase 2. end points will be decided at a later date but most likely progression free survival and other standard statistics. This shouldn’t change if/when we partner. If the trial results are as good as they are currently, we may be able to get away with fewer patients and do it quicker. However it should be noted that Phase 2 patients do not count towards phase 3 trial. LD then mentioned that they need to ‘Talk to the FDA about the trial design’.
MM: Safety study for protocol amendment for MHRA to include iSCIB1+
LD: Main issue was whether we needed to do a new toxicity study, even though it was 90% similar backbone to SCIB1. They [the MHRA] were very comfortable with the safety profile of SCIB1 in patients currently, and were happy to proceed with this without the need for any further data. They were amenable but it took a bit longer than we had hoped.
Presentation link for those able to join. I sadly am travelling today, so most likely wont be able to listen till later.
https://www.lsegissuerservices.com/spark/ScancellHoldings/events/f581274b-146c-4a89-af15-05bcae874775
C11,
Remember with clinical trials once an amendment has been approved by a research ethics committee or the MHRA, it then has to be processed by individual site clinical trials managers and approval granted before it is allowed to cascade down through clinical teams.
This means it’s highly dependent on site clinical trials units and staffing time to make changes. Only once changes are approved can sites start recruiting patients.
We had an amendment approved in September 2019 for a trial across 20 sites, it took nearly till February (just pre-pandemic) to get it approved and through site systems across all sites.
Chester
There is a kind of blinkered view that mRNA is the way forward. That's where the money is and that's why the scientific talent is being drawn towards it.
I agree, we see it here in the UK. Vast amounts of money being put into mRNA technologies. I wonder whether we are putting all our eggs in a single basket and may live to regret that. One of the other striking things is the patent space in this area especially around lipid nanoparticle, ionisable lipids used in these. Many companies have patented these delivery systems and so hold huge sway over the entire modality.
In late stage cancer tumours Modi1 in monotherapy has found it difficult to mount enough of an attack to overcome the vastly mutated micro-biome. It would be very interesting to see how it performed at a much earlier phase of a tumours development.
I agree. The problem you have though is proving a phase 1, first in human compound is better than the existing treatments. Early stage patients have many more options and so from a risk profile, it makes no sense to try a new novel treatment. Hence Scancell have to prove it works in more difficult patient populations, before they have any hope in moving to earlier stage patients.
Do you agree that it's because Scancell are having to start with the most difficult stage cancers that we are flying so under the radar.
Partially (see comment above), but I also think many clinicians and researchers are cautious about DNA based vaccines due to the possibility of integration which in itself can cause cancers, hence their love for the transient mRNA vaccines. I also suspect on the moditope front a reluctance because it’s very novel - targeting stress induced post-translational modifications. Scancell will be the first.
I see GlymAbs having a lot of interest, especially if the platform can produce more antibodies against different targets. Avidimab, I see could have a lot of interest, but only if people see a value in using it on their own antibody therapeutics, if you take say a 80% performing mAb and make it work 82%, then no real point adding Avidimab. However if you have a great target but mAb only works say 50%, if you can get that to 80% with Avidimab, then it would be worth licensing.
I’m curious as to whether we will see licensing deals over the coming months/years.
Some interesting take home points. As I have suspected, SCLP may be more under the radar than we realise/hope. I wonder if part of the reason moderna has gone after resectable melanoma is because they have access to clinical material to enable sequencing and neoantigen identification on. Without that, you would struggle to identify which targets to go after.
I have received a response back to the email I sent, which has some really interesting and insightful views.
Burble: We saw during covid that mRNA vaccines, due to their inherent stability issues require low-temperature cold supply chains. Do you think there is any potential in this space for us to move away from mRNA based vaccines and look at other nucleotide formats such as a DNA based vaccines which would require less of this end to end cold chain?
I am not sure we have optimized vaccines with the mRNA approach. It is certainly worth continuing to look at other approaches, but mRNA has features (safety, ease of development, built in adjuvants with lipid nanoparticles as well as inherent “danger signal” of free mRNA) that make it an excellent vaccine format.
Burble: Do you think we will ever have the opportunity to move towards a more ‘one size fits all’ approach with this type of cancer vaccine rather than needing to make a bespoke vaccine for each individual patient. From a manufacturing perspective this would help reduce cost and the time it takes to manufacture?
Maybe. I think we will be able to make better tumor specific antigen vaccines targeting shared antigens. Whether these are better than personalized neo-antigen approach will need to be sorted out in randomized trials. Life will be good if we have to run those trials, since it will mean that both approaches help people.
Burble: From a clinical perspective, what do you see as the challenges/opportunities within this space going forward?
Roll out is a challenge. Having useable tissue that yields high-enough quality mRNA and DNA to run the sequencing to inform vaccine development is not a given. This will be the biggest issue from an individual patient perspective. The manufacturing issue is overcome-able, but obviously it would be much easier to have an as effective, off-the-shelf vaccine with similar or greater efficacy.
Burble: My final question comes more from my own curiosity. Do we see recurrence in these patients, or do patients who respond well to treatment have long-term protection from metastasis due to the T-cells generated being on surveillance around the body for other metastases?
There are certainly patients who recur, but it seems that recurrences distantly are dramatically lower, suggesting that there is a better anti-tumor memory population of T cells generated.
I finally managed to get my hands on the following publication https://aacrjournals.org/cancerdiscovery/article-abstract/13/6/1278/726966/mRNA-Vaccine-Slows-Melanoma-RecurrencemRNA-Vaccine?redirectedFrom=fulltext 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.
Dracula,
Yes SCLP is trialling a different method. The process of generating and using a CAR-T involve harvesting a patient's T-cells, then genetically modifying them in the lab to generate the T-cell. Then reinfusing this back into the patient where it gets to work tackling the patients malignancy.
In both the immunobody platform and the moditope platform, the T-cells are generated using the natural mechanisms that exist in the immune system. In the case of immunobody, the DNA platform is translated and transcribed into proteins which contain the appropriate cancer epitopes (targets). The immune system is presented with these and then generates T-cells against these targets.
In the case of moditope, short modified peptides are presented to the immune system which then generates T-cells against these targets.
So unlike CAR-T cells, you're not doing this in a lab. You're just using the patient's own immune system to do the job for you. So v.different. Therefore the news coming from the CAR-T world is interesting, but shouldn't really concern scancell.