Member Info for KonarA

Regarding isicb1

"If positive, data generated by iSCIB1+ could lead to the initiation of a potential, rapid clinical development programme in H2 2024. An adapted registration trial could yield Phase 2 data within 2 years and would provide the Company with a pathway to a potential deal. The Phase 3 data could be complete within the following 3 years."

Scancell have previously said they would be looking to partner this up at the end of this trial. Now they are talking about the two year data providing a pathway to a deal with a subsequent registration trial. Does anyone else think this whole paragraph above reads like a deal in principle is in place contingent on the iscib1 results?

Today's RNS seemed to have the new chairman's fingerprints all over it. Criticism of Scancell in the past is the failure to focus on the commercial side of the business, and instead wanting to progress anything and everything scientifically. Seems much more of a focus now on being realistic and pragmatic on the things they need to do to become a self sustaining biotech. If I was speculating, I would guess that one of the major shareholders are behind this drive.

"the Company believes that combination therapy with checkpoint inhibitors, which are not currently approved for the treatment of ovarian cancer, could further improve outcomes for this patient group. Evaluation of Modi-1 plus checkpoint inhibitors in other tumour types in the ongoing Phase 1/2 study, will provide supporting data for this proposed combination use."

If the results from the other studies support a combination trial in ovarian cancer, this could be a double gamechanger. Great for the patient's who cannot currently use CPIs, but also a gamechanger for the sales of CPIs if they can get approval for use in combination with moditope. Could be a very strong argument for the hem to buy up the modi platform.

Https://www.scancell.co.uk/frankfurt-listing

My own view on this is that the web site is fully geared towards the combination study, and shouldn't be taken to mean that the monotherapy arm is necessarily fully recruited (although it probably is in ovarian).

The monotherapy arm are people without treatment options (CPIs not approved or ineffective) - in those cases it is very easy to convince someone to try an early stage experimental drug.

For people on the combination arm, they already have CPI as standard of care, which brings with it a range of possible serious side effects. I would guess it is significantly harder to recruit patient's to an experimental drug (which theoretically could bring unknown side-effects and no benefit, as well as additional tests and hospital visits) whilst you still have proven treatment options. That's where the additional recruitment materials could be used to encourage people to sign up.

It's for this reason that I think the omission of ovarian cancer from the website does not necessarily mean already fully recruited.

"This study has c138 participants and when my name was put forward by my oncologist there was only one place remaining and three standby places."

I found this particularly interesting. The target numbers are obviously correct (138)., but I wonder if the rest is a misunderstanding or miscommunication. This person obviously has to be in cohort 4, as they have just started treatment. We know that cohort 4 is to dose just 3 people, same as the other run in cohorts. So is this the 3 people on standby that she is referring to - 3 people waiting on standby to go once the safety committee approved the move into cohort 4?

The alternative, and if the statement is taken as fact, then to have fully recruited all 138 people to the trail, and now its just a case of dosing them, then wow! This trial will fly.

Feels a bit like Alan Partridge trying to get another series

https://www.youtube.com/watch?v=zgPF5xtppTs

Full eligibility and exclusion criteria are here:

https://www.clinicaltrials.gov/ct2/show/NCT05329532

just to add to that though.. the significance of finding a safe, well tolerated dose that is showing clinical response in cohorts 1 and 2 should not be overlooked.

https://www.scancell.co.uk/Data/Sites/1/media/publications/posters/aacr_modify-study-poster_march-2023_final-corrected.pdf

@TF Figure 3 on this poster explains it. Cohorts 1 and 2 had a variation in doses (80µg and 400µg) followed by a Dose Selection phase. The patient with partial regression was from cohort 2 (the higher dose). If you look at the "Results" section it says "20 pts (patients) have received Modi-1(v) (3 pts Modi-1v 80µg/peptide, 17 Modi-1 400 µg/peptide)". Cohort 1 was the 80, cohort 2 was the 400, so all the other patients have come from the expansion cohorts. This confirms that the dose selection for the monotherapy cohorts was the same as Cohort 2.

Interestingly, for Cohorts 3 and 4, figure 3 shows they had the option of dosing cohort 3 at either 80µg or 200µg. The table "Fully Recruited Cohorts" shows that Cohort 3 have all been given 200µg. This backs up the reported "no dose limiting toxicity" and they felt confident to go with the higher dose option alongside the CPI for the first time.

So with this context, the title ""Report after completion of monotherapy dose-finding" very very strongly indicates that the content to be discussed are the Cohorts 1 and 2, as they are the only monotherapy cohorts pre dose selection.

Personally I am more keen to see the CPI combination results to date for cohorts 3 and 4.

wtp you missed a word:

"Report after completion of monotherapy dose-FINDING"

Cohort 1 and 2 had variable doses to find the safe dose to expand out into the full monotherapy cohort. These were the "dose-finding" monotherapy cohorts. Hence why I said the other day that the clue is very much in the title. It is a report on cohorts 1 and 2.

All you need to know about the data to be presented is in the title imho.

If the expectation is "melting all tumours and 100% remission" then it will be very easy for investors to see anything less as a "failure"

The reality is that in order to be commercially viable, Moditope just have to offer benefits above current standard of care, that warrants the additional cost of prescribing Moditope. The fact that Moditope has already demonstrated it can halt disease progression in patients that had exhausted treatment options, then it could already have demonstrated the ability to meet that criteria. The question now becomes "by how much" does it exceed standard of care and "in how many indications". That will determine the value of the product.

In the RG options RNS it specifically says they will make 6 monthly announcements on the uptake of the options in the block listing

@Berm - cheers, that seems like a logical explanation

It does seem to suggest that, but that would be a shame. From a theoretical concept you would think patients that have failed to respond to a CPI would be because they have been unable to mount a sufficient immune response to overcome the residual suppression, and the "kick" from moditope could get them over the line?

Looks like a Scancell attempt to pre-scrub patients that could potentially negatively influence their results? (i know all drug developers do this but still..)

It also says:

"Patients with residual disease as measurable by RECIST 1.1 on ongoing standard of care monotherapy CPI (Modi-1 + CPI combination cohorts only)"

Does this not contradict?

I'm not sure we have ever been told the dosing model for combination with CPI. Assuming a number of the patient's will already be established on the CPI so its possible if the MODI is to be given concomitantly, then there could be a delay waiting for the next CPI dose due.

Thanks for that - i wonder why we haven't had an RNS for it?

Lofas - the question was aimed at Berm. I don't recall reading that Cohort 4 was recruiting or had been given the green light, and I have been looking out for it. I was expecting, based on cohort 1 and 2, that cohort 4 would have been recruiting some time back in Feb to March, but I get with the introduction of Checkpoint Inhibitors they may have chosen to go particularly slowly due to CI bringing its own side effect profile. If cohort 4 has actually started recruiting (and I have just missed that news) then that would re-assure me a good deal.